PLoS One. 2017 Aug 31; 12 (8): e0183685. doi: 10.1371 / journal.pone.0183685.
Cook JB1,2, Hendrickson LM1,3, Garwood GM3, Toungate KM3, Nania CV1, Morikawa H1,3.
inahaneloang
Ho tšoana le lithethefatsi tsa tlhekefetso, bohlokoa ba hedonic ea lijo bo nahanngoa, bonyane ka karolo e itseng, ke tsamaiso ea mesostriatal dopamine (DA). Ho ja ka nako e telele tsa lijo tse phahameng tsa lik'halori kapa lithethefatsi tsa tlhekefetso ka bobeli ho lebisa ho fokolisa tsamaiso ea DA. Liphuputso tse ngata li tsepamisitse maikutlo ho liphetoho tsa DAergic ho striatum, empa ha ho tsejoe hanyane ka liphello tsa lijo tse phahameng tsa lik'halori sebakeng sa ventral tegmental (VTA) DA neurons. Kaha dijo tse phahameng tsa khalori li hlahisa mekhoa ea ho fetola joala ea Daergic, ho ka khoneha hore lijo tsena li ka eketsa ts'oaetso ea ho lemala. Leha ho le joalo, lijo tse phahameng tsa khalori li fokotsa phepelo ea psychostimulant le maemo a khethiloeng sebakeng sa litoeba. Ka lehlakoreng le leng, lijo tse phahameng tsa lik'halori li ka eketsa kapa tsa fokotsa ho noa ethanol, empa ha ho tsejoe hore na lijo tse sa jeoang lijo tse sa jeoang (lijo tsa lijo tsa lijo tsa lijo) li ama ho noa ethanol. Phuputsong ea morao tjena, re ne re ja lijo tsa lijo tse nang le bacon, litlhapi tsa litapole, cheesecake, li-cookie, lijo-thollo tsa lijo tsa hoseng, li-marshmallows le likhetho tsa tsokolate ho banna ba malinyane a Wistar bakeng sa libeke tsa 3-4, ho hlahisa phenotype e feteletseng. Pele ho jafeteria lijo tse feptjoang li fokotseha ho fokotsa ho tlosoa ha ethanol libeke tse fetang li-2 tsa liteko, 'me ka nako e khutšoanyane li fokolise lijo tsa sucrose le ho ja. Habohlokoa, lijo tsa ho ja lijo ha li na phello ho ethanol metabolism kapa methapo ea mali ethanol e latelang 2g / kg ethanol tsamaiso. Keha re le liphaephe, re bonts'a hore lijo tsa ho ja lijong li ntlafatsa DA D2 receptor (D2R) ho itšireletsa ho VTA DA neurons. Liphello tsena li bontša hore lijo tse se nang phepo e ntle-tse bakoang ke ho ja haholo li fokotsa ho noa ethanol, 'me li fana ka maikutlo a hore ho eketseha ha motlakase oa D2R VTA ho ka tlatsetsa ho fokolisitsoeng ha pontšo ea DAergic le ho putsa hypofunction e bonngoeng ka botenya.
PMID: 28859110
DOI: 10.1371 / journal.pone.0183685
Lijo tse sa jeoang tsa lijo tse sa jeoeng-tse bakoang ke ho nona hamonate li eketsa D2 receptor autoinhibition sebakeng sa ventral tegmental le ho fokotsa ho noa ethanol.
PLoS One. 2017 Aug 31; 12 (8): e0183685. doi: 10.1371 / journal.pone.0183685. eCollection 2017.
Cook JB1,2, Hendrickson LM1,3, Garwood GM3, Toungate KM3, Nania CV1, Morikawa H1,3.
inahaneloang
Ho tšoana le lithethefatsi tsa tlhekefetso, bohlokoa ba hedonic ea lijo bo nahanngoa, bonyane ka karolo e itseng, ke tsamaiso ea mesostriatal dopamine (DA). Ho ja ka nako e telele tsa lijo tse phahameng tsa lik'halori kapa lithethefatsi tsa tlhekefetso ka bobeli ho lebisa ho fokolisa tsamaiso ea DA. Liphuputso tse ngata li tsepamisitse maikutlo ho liphetoho tsa DAergic ho striatum, empa ha ho tsejoe hanyane ka liphello tsa lijo tse phahameng tsa lik'halori sebakeng sa ventral tegmental (VTA) DA neurons. Kaha dijo tse phahameng tsa khalori li hlahisa mekhoa ea ho fetola joala ea Daergic, ho ka khoneha hore lijo tsena li ka eketsa ts'oaetso ea ho lemala. Leha ho le joalo, lijo tse phahameng tsa khalori li fokotsa phepelo ea psychostimulant le maemo a khethiloeng sebakeng sa litoeba. Ka lehlakoreng le leng, lijo tse phahameng tsa lik'halori li ka eketsa kapa tsa fokotsa ho noa ethanol, empa ha ho tsejoe hore na lijo tse sa jeoang lijo tse sa jeoang (lijo tsa lijo tsa lijo tsa lijo) li ama ho noa ethanol. Phuputsong ea morao tjena, re ne re ja lijo tsa lijo tse nang le bacon, litlhapi tsa litapole, cheesecake, li-cookie, lijo-thollo tsa lijo tsa hoseng, li-marshmallows le likhetho tsa tsokolate ho banna ba malinyane a Wistar bakeng sa libeke tsa 3-4, ho hlahisa phenotype e feteletseng. Pele ho jafeteria lijo tse feptjoang li fokotseha ho fokotsa ho tlosoa ha ethanol libeke tse fetang li-2 tsa liteko, 'me ka nako e khutšoanyane li fokolise lijo tsa sucrose le ho ja. Habohlokoa, lijo tsa ho ja lijo ha li na phello ho ethanol metabolism kapa methapo ea mali ethanol e latelang 2g / kg ethanol tsamaiso. Ha re le liphateng tsa mahareng, re ile ra bontša hore lijo tsa ho ja lijo li ntlafatsa DA D2 receptor (D2R) autoinhibition ho VTA DA neurons. Liphello tsena li bontša hore lijo tse se nang phepo e ntle-tse bakoang ke ho ja haholo li fokotsa ho noa ethanol, 'me li fana ka maikutlo a hore ho eketseha ha motlakase oa D2R VTA ho ka tlatsetsa ho fokolisitsoeng ha pontšo ea DAergic le ho putsa hypofunction e bonngoeng ka botenya.
PMID: 28859110
DOI: 10.1371 / journal.pone.0183685
Tlhaloso: Cook JB, Hendrickson LM, GM ea Garwood, KM Toungate, Nania CV, Morikawa H (2017) Lijo tse sa jeoang tsa lijo tse bakoang ke ho nona haholo li eketsa D2 receptor autoinhibition sebakeng sa ventral tegmental le ho fokotsa ho noa ethanol. PLoS ONE 12 (8): e0183685. https://doi.org/10.1371/journal.pone.0183685
mohlophisi: James Edgar McCutcheon, Univesithing ea Leicester, UNITED KINGDOM
Re amohetse: Kajeno 24, 2017; E amohetse: August 9, 2017; E phatlalalitsoe: August 31, 2017
Copyright: © 2017 Cook et al. Ena ke sehlooho se bulehileng sa ho kena se tsamaisoang ka tlas'a maemo a License ea Boikarabelo ba Creative Commons, e lumellang hore ho sebelisoe, ho abeloa, le ho beleha ho sa sebelisetsoe, ho fana ka moqapi le mohloli oa pele.
Ho fumaneha ha Data: Lintlha tsohle tse nepahetseng li ka hare ho pampiri le lifaele tsa eona tsa Tšehetso.
Lithuso: Mosebetsi ona o ne o tšehetsoa ke RO1 AA015521 (HM), F32AA021640 (LMH), le T32-AA007471 (Univesithi ea Texas e Austin, Lefapha la Pharmacology le Toxicology, Koleji ea Pharmacy). Lichelete tsena li ne li lefshoa ke Mokhatlo oa Sechaba oa Tlhekefello ea Joala le Tahi. https://www.niaaa.nih.gov/. Bafani ba lichelete ba ne ba se na karolo mosebetsing oa ho etsa lipatlisiso, ho bokelloa ha data le tlhahlobo, ho etsa qeto ea ho phatlalatsa, kapa ho lokisetsa buka eo.
Lithahasello tse tsitsitseng: Bangoli ba boletse hore ho na le lithahasello tsa tlhōlisano tse teng.
Selelekela
Lintho tse matlafatsang lithethefatsi tse lemalloang le lijo tse hlabosang ke karolo e 'ngoe, ke karolo ea tsamaiso ea mesostriatal dopamine (DA) [1]. Ho phaella moo, ho eketsa lithethefatsi tsa tlhekefetso, ho kopanyelletsa le ethanol, kapa lijo tse matla tse matlafatsang li hlahisa li-neuroadaptations tse tšoanang tsa DAergic. Ka mohlala, ho pepesehela ethanol le mefuta e meng ea lithethefatsi hampe ho fokotsa li-receptors tsa D2 (D2Rs) le maemo a basal DA ho statum [2-4], e boetse e bonoa ka matla a sebelisoang matla a matla a lijo [5-7]. Batho ba nang le batho ba bangata ba boetse ba fokolitse polelo ea D2R ho striatum [8] le ho fokotsa ts'oaetso e hlaselang ka lebaka la lijo tse monate [9]. Ka lebaka leo, ho tloha ha li-neuroadaptations li latela lijo tse matla haholo kapa likokoana-hloko tse sa foleng li le joalo, ho ja matla a mangata a matla ho ka eketsa ho lemala lithethefatsi. Ho thahasellisang ke hore lipatlisiso tsa litoeba li bontšitse hore mafura a mangata kapa ts'ebetso ea tsoekere e fokotsa ho noa ha psychostimulant le boemo bo khethiloeng sebakeng seo [10-13]. Ka lehlakoreng le leng, pele ho mafura a mafura kapa tsoekere / lik'habohaedreite li ka eketsa [14, 15] kapa fokotseha [16, 17] ho noa ethanol ka litoeba. Leha ho le joalo, ha ho tsejoe hore na ho sebelisoa ha lijo tse se nang phepo e ngata hangata ho bakoang ke batho ho ama bothata ba ho noa ethanol.
Naheng ea US hoo e ka bang 35% ea batho ba baholo le 17% ea bana le bacha ba boima haholo [18]. Ho ata ho eketsehileng ha botenya ho 'nile ha amahanngoa le ho ba le phihlelo e eketsehileng ea "lijo tse sa jeng lijoana" tse mafura, tsoekere le lik'habohaedreite tse ling [19], 'me ho sebelisoa ha lijo tsena ho hlahella haholo nakong ea bocha [20-22]. Ka boiteko ba ho etsisa mofuta ona oa matla a matla a lijo tse matlafatsang ho tlatsetsang botenya, bafuputsi ba fane ka likhoto ho fumana lijo tse sa jelloang ke lijo tse sa jeseng lijo, tse bitsoang lijo tsa ho ja lijo [5, 6, 23]. Ho fanoa ka lijo tsa lijo tsa lijo tsa lijo tse fokolang lijo tse fokotsang D2R le litekanyetso tsa basal DA ho statum, ho fokotsa kutloisiso ea potoloho ea moputso ho sebelisa mokhoa oa ho itšireletsa, le ho hlahisa lijo tse qobelloang [5, 6]. Leha ho le joalo, ha ho tsejoe hore na ho ja lijo tsa lijo ho fepa lihlahisoa tsa electrophysiological tsa DA neurons sebakeng sa ventral tegmental (VTA) kapa tšusumetso ea ho noa ethanol.
Somatodendritic DA e lokolloa e kopa D2Rs ho somata le dendrites ea DA neurons e hlahisang ho itšireletsa Ka vivo [24, 25] le a vitro [26, 27] ka ho kenyelletsa litsela tsa potassium tse ntseng li lokisoa ka hare (GIRK) ka Gi / o ho bontša. Ka hona, ts'ebetso ea D2R ea GIRK e fella ka hyperpolarization le ho fokotsa monate oa excurability [28]. Li-neurons tsa VTA tsa DA, ho laola khafetsa ea ethanol kapa tsamaiso e matla ea cocaine ho eketsa auto -hibition ea D2R-mediated [29, 30]. Ho phaella moo, ho latela tsamaiso ea li-ethanol ka makhetlo a mangata, keketseho ea D2R ho itšireletsa ho ne ho amahanngoa le ho noa ha ethanol e eketsehileng ea malapa [29]. Le hoja ho hlakile hore lijo tse phahameng tsa lik'halori li hlahisa lik'hemik'hale tsa DAergic tse lemalloang, liphello tsa lijo tse phahameng tsa lik'halori ho D2R ho itšireletsa ka VTA DA neurons ha e tsejoe.
Phuputsong ea morao tjena, re ile ra batlisisa liphello tsa lijo tsa ho ja lijo tsa motlakase ethanol kapa sucrose ho noa, VTA DA neuron basal firing frequency, le autoinhibition e entsoeng ka D2R ea VTA DA neurons. Ho ja lijo tsa motsoako oa lijo nakong ea bocha ho etsa hore ho be le bo-mpoli bo kang bo-phenotype le ho fokotsa nako e telele ea ho noa ethanol ho sebelisa 2 hr ho noa lefifing (DID) ethanol tlhahiso e hlahisang ethanol e kenang. Habohlokoa, ho ja lijo tsa ho ja lijo ha ho na tšusumetso ea mali ethanol (BECs) kapa ethanol metabolism rate ka mor'a 2 g / kg intraperitoneal (ip) ente ea ethanol. Ho feta moo, lijo tsa ho ja lijo tsa lijo tsa lijo li ile tsa eketseha D2R-mediatedhibitations ea VTA DA neurons.
Mekhoa le thepa
LihloohoMatsu a Wistar a fumanoa Harlan laboratories (Indianapolis, IN) libeke tsa 3. Li-rats e ne e le masoha tse neng li lula ka har'a liphaephe tsa Plexiglass, tse ka lehlakoreng le leng la cage li ne li e-na le sethala sa Plexiglass se nang le 7 "x 4" x XUMUMX "e bolokiloeng fatše bakeng sa ho ja lijo tsa lijo. Likokoanyana kaofela li ne li e-na le chow e tloaelehileng ea laboratori e fumanehang ad libitum 'me metsi a ne a fumaneha ka linako tsohle ntle le ha ethanol kapa sucrose li noa joala. Seboholi se ne se ts'oaroa ka morao 12 hr leseli-lefifi (leseli le qala ho 0100 hr), mocheso o tsitsitseng oa 22 ± 2 ° C, le 65% e amanang le mongobo. Mekhoa ea tlhokomelo ea liphoofolo le tsamaiso ea liphoofolo e ile ea latela Mekhatlo ea Sechaba ea Litaiso tsa Bophelo tlas'a Univesithi ea Texas ho Austin Institutional Animal Care le Komiti ea Ts'ebeliso ea Melao e amohelehang.
Ho ja lijo tsa ho ja lijo
Hang ka letsatsi (1 hr ho potoloho e lefifi) lijo tsa ho jella tse nang le lijo tse se nang 'mele tse nang le lik'halori tse ngata tse kenyeletsang cheesecake (Khamphani ea Atlanta Cheesecake, Kennesaw, GA), bacon (HEB, San Antonio, TX), cookies (Chips Ahoy / Oreo, Nabisco, East Hanover, NJ; lijo tse nang le tsoekere, Vista, Lijo tsa Sheare, Massillon, OH), likhase tsa litapole (Lays Classic / Ruffles, Frito Lay, Plano, TX) lijo-thollo tsa lijo tsa hoseng tse tsoekere haholo (CoCo Puff, General Mills, Minneapolis, MN; Froot Loops, Kellog, Battle Creek, MI), marshmallows (Kraft, Northfield, IL), kapa lipompong tsa chokolete (M&M, MARS, McLean, VA) e fuoe sehlopha sa lijo tsa ho jella. Lijo tse 'ne tsa lijo tsa ho jella li ne li tsamaisoa ka letsatsi mme mefuta e fapaneng ea lijo e ne e bolokoa ka ho fapanyetsana lijo tsa letsatsi le letsatsi. Sehlopha sa chow feela se amohetse chow ea laboratori feela (LabDiet, Prolab RMH 1800, St. Louis, MO), e neng e fumaneha le ho sehlopha sa lijo tsa ho jella ad libitum. Likahare tsa Macronutrient (tse ipapisitseng le likhalori tse fanoeng) tsa chow feela li ne li na le mafura a 14%, 65% khabohaedreite le 21% ea protheine, 'me ka karolelano lijo tsa ho jella li ne li na le mafura a 42%, 52% khabohaetereite le 6% ea protheine. Lijo tsa ho jella li ile tsa fuoa libeke tse 3 bakeng sa ho sebelisoa ha kalori le liteko tsa kantle tsa D2R tsa kantle (ho qala ka libeke tse ka bang 3-4) le bakeng sa libeke tse 4 bakeng sa liteko tse ling tsohle (ho qala ka libeke tse ka bang 5). Bakeng sa litekanyo tsa phepelo ea `` caloric '', lijo tsa ho jella le lijo tsa chow feela li ne li lekanngoa letsatsi le leng le le leng 'me lijo tsa caloric li ne li baloa ho sebelisoa tlhaiso-leseling ea macronutrient e fanoeng ke moetsi.
Homecage ethanol kapa sucrose ho noa
Beke e 'ngoe ka morao ho tloaeloa, litsie li ile tsa fuoa 2 hr / letsatsi likhaello tse fokolang tsa ethanol (10% v / v) kapa srorose (5% w / v) tharollo ea ho hlahloba ho noa joala. Nakong eohle ea ethanol kapa sucrose ho noa ho hloekisoa ha metsi ho ile ha nkeloa sebaka ke botlolo e nang le tharollo ea ethanol kapa ea sucrose ka 1 hr ho potoloha lefifi. Ho latela ethanol ea pele kapa ts'ehetso ea joala (matsatsi a 7), likhofu li ne li fuoe lijo tsa ho jela kapa lihlopha feela. Ka mor'a moo, likhofu li ne li fepa lijo tsa ho ja lijo kapa likheo feela bakeng sa libeke tsa 4. Lihora tse mashome a mabeli a metso e mene ka mor'a lijo tsa ho qetela tsa ho ja lijo, likhofu li ile tsa qala letsatsi le leng le le leng ethanol kapa sucrose ho noa joala.
Maqhubu a ethanol (BEC)
Ka mor'a libeke tsa 4 tsa lijo tsa motsoako kapa lijo tse fepa feela, likhofu li ne li tsamaisoa ka ethanol (2g / kg, 15% v / v ka saline, ip) 24 hr ka mor'a lijo tsa ho qetela tsa ho ja lijo tsa lijo. Li-samples kaofela tsa mali (10 μL) li ne li bokelloa ka mohatla monoaneng 30, 60, le 120 min ka mor'a hore e hlajoe ke ethanol ebe e kenyelitsoe likhabeng tsa galase tsa khase tsa chromatography (GC) tse nang le 90 μL ea 5M sodium chloride. Mehlala ea ethanol e ile ea hlahlojoa ka letsatsi le tšoanang le ho bokelloa ha mali le GC ho sebelisa Bruker 430-GC (Bruker Corporation, Fremont, CA) e nang le mochine oa ionisation oa mollo le Autosampler ea Combi PAL. Ka bokhutšoanyane, sampula e 'ngoe le e' ngoe e ne e futhumala ho 65 ° C bakeng sa minara ea 3 pele fiber e sebetsang ka matla e tiileng (SPME; 75 μm CAR / PDMS, silika e fokolang; Supelco) e noa mouoane oa ethanol bakeng sa 3 min. Sesebelisoa sa SPME se ntan'o tlosa sesebelisoa hore e be sekepe sa injection ea GC bakeng sa 1 min ho 220 ° C. Helium (8.5 mL / min e phallo ea metsotso) e ne e sebelisoa e le mokelikeli oa tšepe le HP Innowax capillary column (30 mx 0.53 mm x 1 μm lebelo la filimi; Agilent Technologies, Santa Clara, CA) e ne e sebelisetsoa ho arohana. Litekanyetso tsa ethanol tsa ka ntle (25, 50, 100, 200, 400, le 600 mg / dL) li ile tsa hlahlojoa ho bala sekhahla se tloaelehileng. Chromatograms li ne li hlahlojoa ka mokhoa oa CompassCDS Workstation software (Bruker Corporation, Fremont, CA), le nako e phahameng ea ethanol (~ 2 nako ea ho boloka nako) e sebelisitsoe ho etsa sekhetho se tloaelehileng sa li-ethanol.
Electrophysiology
Li-rats li ne li sa sebelisetsoe ke isoflurane 'me boko bo ile ba tlosoa' me ba arohanngoa tharolong ea serame e nang le (mM) 205 sucrose, 2.5 KCl, 1.25 NaH2PO4, 7.5 MgCl2, 0.5 CaCl2, Glucose ea 10 le 25 NaHCO3, e tletse ka 95% O2, le 5% CO2 (~ 300mOsm / kg). Lihlahisoa tsa Horizontal midbrain (200 μm) li ne li arotsoe vibitome 'me li lumelloa hore li hlaphoheloe hr XMUMX hr mokelikeli oa maiketsetso (aCSF) ho 1 ° C. Litlaleho li ne li etsoa ka morao-rao VTA 34-50 μm ho tloha moeling o ka hare ho mokokotlo o ka hare ho seteishene sa optic. Nakong ea ho ngolisa, lilae li ne li sebelisoa hampe ka oksijene, e futhumetseng (150 ° C) aCSF (ka mM) 34 NaCl, 126 KCl, 2.5 NaH2PO4, 1.2 MgCl2, 2.4 CaCl2, Glucose ea 11, NaHCO 21.43. Litšoantšo tse sa amaneng le li-cell-attached (~ 20 MΩ seal) li ne li etsoa ka lipipi tse nang le 150mM NaCl. Litlaleho tsohle tsa lisele li ne li etsoa ka lipipipi tse nang le tharollo ea intracellular e nang le (mM) 115 K-methylsulfate kapa K-gluconate, 20 KCl, 1.5 MgCl2, 10 HEPES, 0.025 EGTA, 2 Mg-ATP, 0.2 Na2-GTP, le 10 Na2-phosphocreatine (pH 7.2-7.3, ~ 285 mOsm kg-1). Li-neuron tsa DA tse kentsoeng li ile tsa khetholloa ka ho thunya ha pacemaker (1-5 Hz) le menyetla e pharalletseng ea liketso (> 1.2 ms) ho hlophisitsoeng ka sele, le kholo ea Ih (> 200 pA) ho arabela mohato oa 1.5 sec voltage ho tloha ho -62mV ho isa ho -112 mV ka har'a cell-voltage voltage-clamp mode. Lirekoto tsa li-voltage-clamp li entsoe ka bokhoni ba -62mV bo ts'oaroang, bo lokisitsoeng bakeng sa matla a kopaneng a metsi a -7 mV. Lirekoto tsa lisele tsohle li lahliloe haeba khanyetso ea letoto e eketsehile kaholimo ho 20 MΩ kapa khanyetso ea ho kenya e theohile ka tlase ho 200 MΩ. Boitsebiso bo tlhotliloeng ka 1-5 kHz mme bo fetotsoe ka digitized ho 2-10 kHz.
Tlhahlobo ea lintlha
Litaba li hlalosoa e le tsa bohlokoa ± SEM. Tlhaloso ea sesebelisoa e ne e khethiloe ke teko ea T ea Tlhahlobo kapa litsela tse peli tsa ANOVA e lateloa ke teko ea Bonferroni post hoc.
Results
Ho finyella lijo tsa lijo tsa lijo tsa lijo tsa lijo tsa lijo tsa lijo ho tlisa lijo tse ngata tsa caloric le ho feta-joaloka phenotype
Lijo tsa caloric bakeng sa lijo tsa ho ja le lihlopha feela lihlopha hammoho le mohloli oa lik'hilojule bakeng sa sehlopha sa lijo tsa ho ja lijo li ile tsa hlahlojoa libeke tse ling tsa 3. Sehlopha sa lijo sa ho ja lijo se ja lijo tse ngata ho feta likheo tsa lihlopha tsa 3 tsa ho fepa (ho sebelisana: F(2,62) = 22.43, le <0.0001; lijo: F(1,62) = 17.41, p <0.001; nako F(2,62) = 254.7, p <0.0001; Setšoantšo sa 1A). Sehlopha sa lijo tsa ho ja lijo se ja lijo tse nang le lik'hilojule tse ngata ho tsoa lijong tsa lijo ho feta li-pelts tsa chow ho pholletsa le libeke tsa 3 tsa ho fepa (ho sebelisana: F(2,72) = 57.22, le <0.0001; lijo: F(1,72) = 117.2, p <0.0001; nako F(2,72) = 110.5, p <0.0001; Setšoantšo sa 1B). Li-calories tse nkiloeng ho li-pellets tsa chow li ne li le khōlō haholo ho khetholla feela nakong ea tlhahlobo ea beke ea 3 (ho sebelisana: F(2,62) = 28.80, le <0.0001; lijo: F(1,62) = 196.3, p <0.0001; nako F(2,62) = 150.0, p <0.0001; Setšoantšo sa 1C). Qetellong, sehlopha sa ho ja lijo sa lijo sa lijo se bonts'a boima ba 'mele ho feta libeke tsa 3 tsa ho fepa (ho sebelisana: F(2,62) = 8.188, le <0.001; lijo: F(1,62) = 10.62, p <0.005; nako F(2,62) = 18.48, p <0.0001; Setšoantšo sa 1D). Libeke tse 'nè tsa lijo tsa ho ja lijong li etsa hore ho be le bo-mpo-like-phenotype bo bobebe bo nang le boima ba' mele bo boima ka ho fetisisa ho feta sehlopha feela (ho sebelisana: F(27,2376) = 44.48, le <0.0001; lijo: F(1,2376) = 14.89, p <0.001; nako F(27,2376) = 2634, p <0.0001; 1E ea setšoantšo). Ho phaella moo, ho sehlopha se fapaneng sa liphoofolo re bontšitse hore sehlopha sa lijo tsa ho ja lijo se ja lijo tse nyane haholo nakong ea libeke tsa 4 tsa lijo tsa ho ja lijo tse bapisoang le litaelo (ho sebelisana: F(27,486) = 3.039, le <0.0001; lijo: F(1,486) = 601.7, p <0.0001; nako F(27,486) = 8.097, p <0.0001; Setšoantšo sa 1F). Liphello tsena li bonts'a hore lijo tsa lijo tsa lijo tsa lijo li fella ka ho ja lijo tse ngata tse nang le phepo e ntle haholo le ho lahleheloa ke matla a homeostatic.
Ho kenngoa ha lik'halori le mohloli oa likhalori ho ile ha hlahlojoa ho feta libeke tse 3. (A) Likhoto tse nang le phihlello ea letsatsi le letsatsi lijong tsa phepelo li ja li-calories tse ngata nakong ea libeke tse 3 tsa phepo ho feta sehlopha sa chow feela (n = 14-19 / group). (B) Sehlopha sa lijo tsa ho jella se jele li-calories tse ngata haholo ho tsoa lijong tsa phepelo ho feta li-chowelle (n = 19). (C) Sehlopha sa chow feela se ne se ja likhalori tse ngata ho tsoa ho li-chowelle ho feta sehlopha sa lijo tsa ho jella (n = 14-19 / sehlopha). (D) Ho fihlella lijo ka mokhoa oa ho jella ho felletse ka ho eketsa boima ba 'mele ho feta libeke tse 3 tsa phepo (n = 14-19 / sehlopha). (E) Libeke tse 'ne tsa lijo tsa ho jella li fepa haholo ho eketsa boima ba' mele, ha li bapisoa le li-chow feela tse laoloang (phello e kholo ea phepo, p <0.001, ANOVA, n = 44-46 / sehlopha) (F) Ho pholletsa le libeke tsa 4 tsa phihlello ea lijo tsa ho jella, sehlopha sa lijo tsa ho jella se ja chow e fokolang haholo ho feta sehlopha sa chow (phello e kholo ea phepo, p <0.0001, ANOVA ea litsela tse peli, n = 10-11 / sehlopha). * p <0.05, ** p <0.01, *** p <0.001, tlhahlobo ea poso ea Bonferroni.
https://doi.org/10.1371/journal.pone.0183685.g001
Pele ho jafeteria lijo tse feptjoang li fokotsa ho noa ethanol ho noa ho se nang phello ho ethanol metabolism rate kapa BECs
Ho fumana hore na liphello tsa lijo tsa pele tsa ho ja lijong tsa pele li fetile ka ho noa ethanol re ne re sebelisa ethanol DID 2hr e fokolang ho fumanoa habonolo ea ho noa (bottle e le 'ngoe, 10% v / v) ea ho noa e hlahisang ethanol e kenang. Ho noa ethanol ho noa (g / kg) ka kakaretso matsatsing a 7 pele ho lijo tsa lijo tsa lijo tsa lijo ho ne ho le joalo pakeng tsa lihlopha (t(11) = 0.3295, p = 0.7480; Setšoantšo sa 2A). Leha ho le joalo, ka mor'a libeke tsa 4 tsa lijo tsa ho ja lijo, phepo eohle ea ethanol e ne e fokotseha nakong ea libeke tsa 2 tsa teko (lijo: F(1,143) = 5.635, p <0.05; nako F(13, 143) = 3.638, p <0.0001; Setšoantšo sa 2B). Boholo ba ho fokotsa ho noa ethanol e ne e le khōloanyane ha ho kenngoa li-ethanol ka g / kg ho tloha ha litekanyo tsa 'mele tsa lijo tsa ho ja le ho ja lihlopha feela li fapane haholo. Ethanol e kenngoa ka g / kg ka nako ea libeke tsa 2 tsa teko e ne e le 0.67 ± 0.11 g / kg bakeng sa sehlopha se le seng feela le 0.25 ± 0.06 g / kg bakeng sa sehlopha sa lijo tsa ho ja lijo. Tšebeliso ea metsi ka libeke tsa 2 tsa teko e ne e sa fapane pakeng tsa lihlopha (ho ja: F(1,143) = 0.1280, p = 0.7273; Setšoantšo sa 2C).
(A) Ho bolela ho noa ha ethanol ea mantlha (g / kg) matsatsing a 7 pele ho fepa lijo tsa ho jella ho ne ho tšoana lipakeng tsa lihlopha (p = 0.7480, t-test ea Seithuti, n = 6-7 / sehlopha). (B) Pele ho fepa lijo tsa ho jella (libeke tse 4) ho fokolitse palo eohle ea ethanol (10%, v / v, 2hr / letsatsi) e jeoang nakong ea libeke tsa 2 tsa liteko (phello e kholo ea phepo, p <0.05, ANOVA ea litsela tse peli , n = 6-7 / sehlopha), (C) ntle le phello ea ts'ebeliso ea metsi kaofela (n = 6-7 / sehlopha). (D) Ho ne ho se na phapano matsoapong a li-BEC (30-120 min ho latela tsamaiso ea 2g / kg, ip) lipakeng tsa lihlopha (p = 0.6535, regression regar, n = 4-5 / group). Li-BEC li ne li ts'oana lipakeng tsa lihlopha ho 30, 60, le 120 min post-ethanol tsamaiso. BEC, mahloriso a ethanol ea mali; ip, intraper.
https://doi.org/10.1371/journal.pone.0183685.g002
Ho tloha ha lijo tsa ho ja li fepa li ka fetola mekhoa ea metsolico, ho akarelletsa le ethanol metabolism, re ne re tsamaisa ethanol (2g / kg, ip) mme re lekanya BECs ho 30, 60, le 120 min post-injection ka mor'a lijo tsa lijo kapa lijo tsa ho fepa feela. Ho sebelisa marotholi a lekaneng ho bapisa li-slope BEC (30-120 min post-injection) pakeng tsa lihlopha, ho ja lijo tsa ho ja lijo ha ho na phello ho ethanol metabolism rate (p = 0.6535; Setšoantšo sa 2D). Ho feta moo, ho ne ho se phapang ho li-BEC pakeng tsa lihlopha (ho ja: F(1,14) = 2.056). Ka lebaka lena, liphetoho tsa methapo ea ethanol metabolism kapa ethanol e kenngoa maling a ke ke a hlalosa ho noa ha ethanol e fokotsehang ka mor'a lijo tse jang lijo.
Pele ho jafeteria lijo tse feptjoang li fepa ka tsela e fetotsoeng li-homroage sucrose ho noa le ho ja lijo
Ho etsa qeto ea hore na lijo tsa lijo tsa motlakase li fetola tšebeliso ea lits'ebetso tse ling tse matlafatsang seo re ileng ra se hlahloba liphello tsa lijo tsa pele tsa ho ja lijo tse fanang ka lijo tsa malapa. Ho sebelisa mokhoa o tšoanang oa DID 2hr o fokolang ho finyella li-sucrose (sekoti se le seng, 5% w / v) ho noa joala, baseline sucrose ho noa (mL / kg) e ne e le pakeng tsa lihlopha (t(29) = 0.4600, p = 0.6489; Setšoantšo sa 3A). Pele ho phomolo ea lijo ho fepa ka tsela e fokolang ho fokotsa ho noa joala (sesebelisoa x nako ea ho buisana: F(13,377) = 2.520, p <0.005; Setšoantšo sa 3B). Le hoja ho ne ho e-na le lijo tse ngata x ho sebelisana ha nako, tlhahlobo ea poso ha ea ka ea fihla ka nako leha e le efe. Leha ho le joalo, ho itšetlehile ka data (Setšoantšo sa 3B), ho sebelisana pakeng tsa sehlopha sa lijo le nako ho ka hlalosoa ka ho fokotseha ha nakoana ho sucrose ho noa ho latela lijo tsa ho ja lijo. Ka bekeng ea bobeli ea teko, leha ho le joalo, sucrose ho noa e ne e tšoana le sehlopha sa sehlopha feela. Tšebeliso ea metsi ka libeke tsa 2 tsa teko e ne e sa fapane pakeng tsa lihlopha (ho ja: F(1,377) = 1.176, p = 0.2870; Setšoantšo sa 3C). Ho tšoana le thuto ea pele [31], lijo tsa ho ja lijo tse fokotsang lijo tse fokotsang lijo tse fokolang (chobelisano: F(6,110) = 12.46, le <0.0001; lijo: F(1,110) = 15.46, p <0.005; nako F(6,110) = 10.97, p <0.0001; Setšoantšo sa 3D) matsatsi a 2 ka mor'a ho fepa lijo tsa ho jella (Bonferroni posthoc test, p <0.001; Setšoantšo sa 3D). Ka lebaka lena, ho ja lijo tsa motsoako oa lijo ho etsa hore ho be le ho fokotsa nako e telele ho noa ethanol le ho fokotsa nako e khutšoanyane ea sucrose ho noa le ho ja lijo.
(A) Boemo ba mantlha ba seno sa sucrose se nooang (mL / kg) matsatsing a 7 pele ho phepo ea phepo ea lijo li ne li tšoana lipakeng tsa lihlopha (p = 0.6489, t-test ea Seithuti, n = 15-16 / sehlopha) (B) Pele ho ja lijo tsa ho jella (libeke tse 4) sucrose e fetotsoe nakoana (5%, w / v, 2hr / day) ts'ebeliso (ja lijo x nako ea tšebelisano, p <0.005, ANOVA ea litsela tse peli, n = 15-16 / sehlopha) . (C) Ho ne ho se na phapang lipakeng tsa ts'ebeliso ea metsi lipakeng tsa lihlopha (n = 15-16 / group). (D) Pele ho lijo tsa ho jella ho fepa nakoana ho fokotsa ho ja ha chow (n = 10 / sehlopha). *** p <0.001, tlhahlobo ea poso ea Bonferroni.
https://doi.org/10.1371/journal.pone.0183685.g003
Ho ja lijo tsa ho ja lijo ho eketsa D2R autoinhibition ho VTA DA neurons
Slice ea brain electrophysiology e ne e sebelisetsoa ho hlahloba liphello tsa lijo tsa ho ja lijo tse fokolang motlakase oa basal le sekhahla sa D2R-mediinhibition ea VTA DA neurons. Ho fepa lijo tsa ho ja lijo ha ho na phello ho basal tonic pacemaker moferefere oa VTA DA neurons (t(72) = 0.7294, p = 0.4681; Setšoantšo sa 4A le 4B). Ka mor'a moo, re ile ra leka liphello tsa lijo tsa ho ja lijo ka metsing a tsoang ka ntle ho D2R re sebelisa D2R agonist quinpirole. Ho ja lijo tsa ho ja lijo ho ja lijo tse eketsehileng ho eketsa ho ba le tlhōrō ea boholo ba methapo ea li-quinpirole (100nM).(39) = 3.167, p <0.005; Setšoantšo sa 5A) ho bapisoa le taolo. Ho feta moo, ho ja lijo tsa ho ja lijo ho eketsa liphello tse thibelang ho ba le 10nM quinpirole ka makhetlo a mangata a VTA DA neurons nakong ea 10 min ea tsamaiso ea quinpirole (ho sebelisana: F(19,513) = 5.425, le <0.0001; lijo: F(1,513) = 16.40, p <0.0005; nako F(19,513) = 39.24, p <0.0001; Setšoantšo sa 5B), le karolo ea lekholo e thibelang ho ferefetsa maqhubu a hlahisoang ke quinpirole (t(27) = 3.824, p <0.001; Setšoantšo sa 5C). Ha ho e-na le maqhubu a phahameng a quinpirole (30nM) ho ne ho se na phapang ho thibela palo ea ho thunya nakong ea 10 min ea tsamaiso ea quinpirole (lijo: F(1,304) = 0.1049, p = 0.7502; Setšoantšo sa 5D) kapa lekholong ho thibela ho thunngoa pakeng tsa lihlopha (t(16) = 0.05265, p = 0.9587; 5E ea setšoantšo). Ka lebaka lena, ho ja lijo tsa ho ja lijo ho hlahisa li-quinpirole-mediated (100nM) maqhubu a ka ntle 'me ho eketsa kutloisiso ea thibelo ea lipina tsa ho thunya.
(A) Basal tonic ho ferefetsa maqhubu a VTA DA neurons e ne e le pakeng tsa lihlopha (p = 0.4681, teko ea T-test, n = 36-38 / sehlopha). (B) Matšeliso a baemeli ba VTA DA neuron e chesang ka mor'a libeke tsa 4 tsa chow feela (buluu) kapa lijo tsa ho ja lijo tse bofubelu (bofubelu). DA, dopamine; VTA; sebaka sa ventral tegmental.
(A) Ho ja lijo tsa lijo tsa motlakase ho ile ha eketsa tlhōrō ea boholo-holo ea li-quinpirole-mediated (100 nM) e thibelang maqhubu a GIRK ka ntle ho bapisoa le likhohlo feela. Ho hlapa ha quinpirole ho sebelisitsoe 10 min le sulpiride (1 μM) ka potlako e ile ea fetola hona joale e sebelisitsoeng lipakeng tsa quinpirole. Mehlala ea maqhubu a ka ntle a quinpirole (Vh = -62 mV) bakeng sa chow feela (putsoa) kapa lijo tsa ho jella tse fepiloeng (khubelu) likhoto (n = 16-25 / sehlopha). (B) Ho fepa lijo ho jele lijo ho ekelitse litlamorao tsa 10 nM quinpirole ho VTA DA neuron e thunyang khafetsa ho feta 10 min ea quinpirole bath application (phello e kholo ea phepo, p <0.0005, ANOVA, n = 13-16 / sehlopha) le (C) liperesente tsa quinpirole-mediated lipina tsa maqhubu a ho thunya (p <0.001, t-test ea Seithuti). Lits'oants'o tse emelang tsa maqhubu a ho thunya ha neuron ea DA nakong ea ts'ebeliso ea mantlha kapa ts'ebeliso ea 10 nM quinpirole kamora ho sebelisa chow feela (putsoa) kapa phepo ea phepo (khubelu). (DE) Thibelo ea maqhubu a ho thunya ha neuron ea DA ka 30 nM quinpirole e ne e tšoana lipakeng tsa lihlopha (n = 9 / sehlopha). Kamora 10 min ea 30 nM quinpirole bath application, sulpiride (1 μM) e ile ea sebelisoa bathong ho khutlisetsa thibelo e potlakileng ea quinpirole-mediated ea makhetlo a ho thunya. Lits'oants'o tse emelang tsa maqhubu a ho thunya ha neuron ea DA nakong ea ts'ebetso ea mantlha kapa ts'ebeliso ea 30 nM quinpirole kamora ho sebelisa chow (blue) kapa phepo ea phepo (khubelu). *** p <0.001, t-teko ea Seithuti. DA, dopamine; D2R, mokelikeli oa dopamine D2; GIRK, G protein-gated kahare e lokisa metjha ea potasiamo; VTA; ventral tegmental sebaka.
https://doi.org/10.1371/journal.pone.0183685.g005
Puisano
Sepheo sa thuto ea morao-rao e ne e le ho hlahloba liphello tsa ho ja lijo tsa ho ja lijo tsa ho noa ethanol le VTA DA neuron physiology. Pele ho ho jela lijo tsa phepo li fokotsa ho noa ethanol nakong ea libeke tsa 2 tsa teko, empa ha li na phello ho ethanol metabolism rate kapa BECs ka mor'a 2g / kg (ip) tsamaiso ea ethanol. Ho 'nile ha boleloa hantle hore lijo tse phahameng tsa khalori le botenya bo bakoang ke ho ja haholo li etsa hore ho be le pontšo ea DAergic e fokolang, e hlahisitsoeng ho tlatsetsa moeeng [32-34]. Leha ho le joalo, liphello tsa botenya bo bakoang ke ho ja haholo liphatsa tsa lefutso tsa DA neurons ha lia tsejoa. Mona, re bonts'a hore mokhoa o atolositsoeng oa ho ja lijo tsa ho ja lijo o eketsa D2R autoinhibition ho VTA DA neurons, e se nang phello ho basal tonic pacemaker ho ferefetsa frequency ka selae. Ha ho hlake hore na ho eketsa ho fokotsa D2R ho latela lijo tsa lijo ho fokotsa ho noa ethanol, leha ho le joalo, ho eketseha ha DA neuron autoinhibition ho ka tlatsetsa ho putsa hypofunction e bonngoeng ka botenya.
Liphello tsa lijo tsa ho jela li jeoa ka ho noa ethanol
Pele ho jafeteria ho fepa lijo ho ile ha etsa hore ho fokotsehe nako e telele ha ho noa ethanol ho nkiloeng lapeng. Kakaretso ea ethanol e neng e jeoa e fokotsehile bakeng sa libeke tse 2 ka mor'a lijo tsa lijo tse hlahisang lijo. Ho feta moo, lijo tsa ho ja lijo tsa lijo ha li na phello ho li-BEC kapa ethanol metabolism rate ka mor'a 2g / kg ethanol tsamaiso. Ka lebaka leo, ho fokotsa ho noa ethanol ho ke ke ha hlalosoa ka lijo kapa phetoho e bakoang ke boima ba 'mele ethanol metabolism kapa ethanol absorption ea mali. Ho fapana le ho noa ethanol, sucrose ea ho noa le ho ja lijo tse ling e ile ea fokotsoa ka nakoana. Qetellong, ho ja lijo tsa pele ho lijo ho ile ha e-ba le ho fokotseha ha nako e telele ha ho sebelisoa ethanol, ha ho bapisoa le ho fumana moputso oa tlhaho.
E ntse e sa tsejoe hantle hore na ho ja lijo ho ama bothata ba ethanol joang ka litoeba. Ka hona, thuputsong ea morao tjena, likhooe li ne li feptjoa lijo tse nang le lijo tse sa jeseng lijo tse atisang ho jeoa ke batho. Liphetho tsa morao-rao li lumellana le phuputso ea morao-rao e bontšang hore ho ja haholo mafura a bakoang ke ho ja haholo kapa ho ja lijo tse mafura-ho fepa litoeba tse seng ntle ho feta ho bontša ho fokotsa khetho ea ethanol [16]. Hape ho 'nile ha bontšoa lijo tse ngata tse nang le lik'habohaedreite tse tlase ho noa ethanol lireng,17], leha ho le joalo, ho kenngoa ha ethanol ho ne ho lekantsoe nakong ea ho ja lijo. Ka lebaka leo, ho noa ethanol e ka 'na ea fokotseha ho latela litlhoko tsa lik'halori ho e-na le ho fokotsa litšila tsa ethanol. Ka lehlakoreng le leng, pele ho ts'ebeliso ea lijo (matsatsi a 21) kapa lijo tse ngata tse mafura (matsatsi a 7) li bontšitsoe ho eketsa ho noa joala ea ethanol [14, 15]. Liphuputso tsena ka bobeli li sebelisitse 12 hr tlhahiso ea 4-5 ho eketseha ha libaka tsa ethanol (1,2,4,7, kapa 9%) bakeng sa matsatsi a 4 e mong le e mong, e fapaneng haholo le 2 ho fihlela ho 10% ethanol e sebelisitsoeng thuputsong ea hona joale. Ho se lumellane ha liphello tsa lijo tse phahameng tsa lik'halori ka ho noa ethanol ho ka bakoa ke ho se tšoane ha lijo tse nang le limatlafatsi tsa nako ea lijo, nako le nako ea ho ja lijo, ethanol ho noa joala paradigm, kapa mathata / mefuta e tobileng ea liphello.
Liphello tsa lijo tsa ho jela lijong ho D2R autoinhibition
Ho fepa lijo tsa ho ja lijo ho eketsa D2R autoinhibition, e boetse e bonoa ka mor'a ho pheta-pheta phetoho ea ethanol. Laboraka ea rona e 'nile ea bontša hore ho tsamaisoa ha ethanol ka makhetlo a mangata ho eketsa matla a maqhubu a ka ntle a D2R VTA,' me e fokotsa Ca2+ ho itšetleha ka mokhoa o itšetlehileng ka maqhubu ana [29]. Thupong eo, phetoho e ngata ea ethanol e ile ea eketsa liphello tse thibelang ho tsuba habonolo ka makhetlo a mabeli a 10 nM le 30 nM. Leha ho le joalo, ho ja lijo tsa ho ja lijo tse ngata ho eketsa tšenyo e thibelang ea quinpirole ka moferefere oa ho thunya feela nakong ea mahloriso a 10 (Setšoantšo sa 5B le 5C). Le hoja re sa ka ra tseba hore na quinpirole e fetotsoe ke eng ka lijo tsa lijo, liphello tsena li fana ka maikutlo a hore lijo tsa ho ja lijo tse eketsehileng li ile tsa eketsa kutloisiso ea quinpirole ho thibela phetoho ea DA neuron. Tsamaiso e matla ea cocaine (20 mg / kg) e boetse e bontšitsoe hore e ekelletse maqhubu a ka ntle a D2R ka bongata ba nigra pars compacta ea litoeba [30]. Ka lehlakoreng le leng, methamphetamine ea boipheliso e 'nile ea bontšoa ho fokotsa mahlaseli a D2R a VTA, e neng e boetse e le Ca2+ ho itšetlehile ka [35]. Ka lebaka lena, ho fapana le li-neuroadaptations ho striatum moo ho ipapisa le lithethefatsi tsa tlhekefetso kapa lijo tse phahameng tsa khalori ka tloaelo ho fokotsa polelo ea D2R, lithethefatsi tse tobileng tsa tlhekefetso li na le liphello tse fapaneng mahlaeng a lipakeng tsa D2R / GIRK. Re lokela ho hlokomela hore thibelo ea lijo e eketsa ho noa lithethefatsi [36], ho akarelletsa le ethanol [37], 'me e fokotsa boipheliso ba D2R [38]. Kaha ho ja lijo tsa motlakase ho eketsa D2R autoinhibition le ho fokotsa ho kenngoa ha ethanol, ho tla ba bohlokoa ho fumana kamano pakeng tsa ho ja lijo, ho fetoha ha D2R, le ho noa ethanol. Ho tsebo ea rona, ho na le thuto e 'ngoe e le' ngoe feela e ileng ea hlahloba liphello tsa botenya bo bakoang ke ho ja ho tlōla tekanyo ea D2R. Thuputsong eo, ho ja haholo mafura a bakoang ke ho ja haholo ha hoa ka ha fetola liphello tse ka thibeloang tsa tekanyo e le 'ngoe ea quinpirole (3-100 nM) ka tekanyo ea VTA DA ea neuron ka litoeba [39]. Leha ho le joalo, ts'ebetso ea phainage ea quinpirole (3, 10, 30, le 100 nM) e ile ea fella ka ho fokotsa liphello tsa ho thibela ho thunngoa, e leng se entseng hore bangoli ba bolele hore litoeba tse mafura li bonts'a ts'oaetso ea D2R ka potlako ho bapisoa le litoeba tse laolehileng. Ha ho hlaka hore na ho na le phapang efe ka lebaka la ho se lumellane ha lijo tsa ho ja lijo tse nang le likhoho ho fapana le ho ja lijo tse mafura haholo ho litoeba tsa D2R autoinhibition. Liphuputso tse ling li hlokehile ho fumana liphello tsa lijo tse matla haholo tsa matla le phepo e bakoang ke ho ja lijo tse ngata ho VTA DA neurons le DINNXX.
Ha ho hlake hore na ho fokotsa ho noa ethanol kapa liphello tsa electrophysiological li susumelitsoe ke boima ba 'mele bo eketsehileng thutong ea hona joale. Leha ho le joalo, lijo tse phahameng tsa k'halori li ka senya tsamaiso ea DA [13] le ho fokotsa ho noa ethanol [16] ho se be le botenya haholo. Ho eketseha ha maemo ho amahanngoa le liphetoho tsa leptin, insulin le ghrelin, kaofela ha tsona li ka lekanyetsa mosebetsi oa tsamaiso ea DA [40-42]. Ka lebaka lena, re ke ke ra hlokomoloha hore liphetoho tsa mekhoa ea ho fepa homeostatic e ka 'na ea ama liphello. Hape re ke ke ra hlokomoloha monyetla oa hore lijo tsa lijo tsa lijo tse ka jang li ka 'na tsa fetoloa mekhoa ea boitšoaro bo kotsi ho tloha ha ethanol le sucrose ho noa li ne li lekantsoe nakong ea nako ea ho fumana nako ea 2.
Thuto ea morao tjena e fapane le lithuto tsa pele [5, 6] ba hlahlobileng liphello tsa lijo tsa ho ja lijo tsa motlakase tsamaisong ea DA ka ho fana ka lijo tsa ho ja lijo nakong ea bocha ho e-na le ho ba motho e moholo. Ho fumanoa hammoho, boitsebiso bo fana ka maikutlo a hore bocha ba lilemong tsa bocha le bohobe ba lijo tsa batho ba baholo ba fepa lihlahisoa tse fokolang tsamaiso ea DA le ho kenya letsoho ho putsa hypofunction. Le hoja ho sa tsejoe hore na ho ja lijo tsa ho ja lijo ha motho a le moholo ho ama D2R ho itšireletsa joang, tsamaiso ea lithethefatsi tsa tlhekefetso e ka eketsa boloetse ba D2R ha e sebelisoa nakong ea bocha [29] kapa ha u se u le motho e moholo [30].
Boemo ba ho eketseha ha motlakase oa D2R le boemo ba hypodopaminergic ka mor'a ho ja lijo tse jeoang ka ho noa ethanol le boitšoaro bo feteletseng
Ka vivo, ho eketseha ha D2R autoinhibition e ka fokotsa ts'oaetso ea DA neuron e fokolang makhetlo, ka hona, ho fokotsa tsamaiso ea DA le ho kenya letsoho lefats'eng la hypodopaminergic. Thutong ea morao-rao le thuto e fetileng ho laborateng ea rona [29], ha rea ka ra lemoha molumo oa basalic o lekaneng ka slice ha sulpiride e sitoa ho fetola maqhubu a phetoang a DA neuron. Leha ho le joalo, Ka vivo mosebetsi oa li-neurons tsa DA o tsoela pele ho susumelitsoe ke boithaopo ba DA le D2R sebakeng seo. Ka lebaka lena, ho eketseha ha D2R autoinhibition ka mor'a lijo tsa ho ja lijo ho lokela ho lebisa ho fokotsang palo ea libetsa tsa DA tsa li-neurons liphoofolong tse sa tšoaneng, le ho tlatsetsa lefats'eng la hypodopaminergic le nahanoang hore le khanna lijo tse ngata haholo [19]. Ka mokhoa o ts'oanang, bopaki bo bongata bo tsoang lithutong tsa mekhoa ea ho itšireletsa le tsa batho bo entse hore ho be le khopolo ea hore boemo ba hypodopaminergic bo kenya letsoho ho qobella ethanol ho ja '43, 44]. Liphetho tsa morao-rao li eketsa lingoliloeng tse ntseng li hōla tse bontšang lijo tsa ho ja lijo tse hlahisang lijo tse hlahisoang ke Daergic li lemalla ho fetoha li lumellana le boemo ba hypodopaminergic [5, 6]. Le hoja ka nako e telele boemo ba hypodopaminergic bo nkoa e le ho tlatsetsa ho noa ethanol e feteletseng, khoebo ea lijo ea motlakase e bakoang ke ho ja lijo ha e fetole ho eketsa ho noa ethanol. Mosebetsi o fetileng ka laborateng ea rona o bontšitse hore khafetsa ethanol ea tsamaiso e ekelitse D2R autoinhibition, e neng e amahanngoa le ho eketseha ha metsi ethanol ho noa ho litoeba [29]. Phuputsong eo, re fihletse qeto ea hore ho eketseha ha D2R ho itšireletsa ka morao ho latela tsamaiso ea ethanol e tlatsetsa lefats'eng la hypodopaminergic le atisang ho boleloa ka ho sa feleng ha ethanol. Ho kopanngoa, ho bonahala eka ke ntho e utloahalang hore polelo ea boemo ba hypodopamineric e hlahisoang ke matla a sa foleng a matla a junk lijo tse jang li-junk e lebisa boitšoarong bo feteletseng / bo qobelloang bo matlafatsang. Ha e le hantle, ho ja matla a mangata a matla a li-dense ha ho tloaelehileng ho fetolela ho sebelisoa ho feteletseng ha lithethefatsi tsa tlhekefetso, empa ho e-na le hoo, ka tloaelo ho fokotsa ho noa ha lithethefatsi. Bopaki bo fetileng le liphetho tsa morao-rao li tšehetsa sena kaha ho atolosoa ho eketsehileng ha lijo tsa ho ja lijo ho etsa hore motho a je lijo tse lekaneng [6], empa e fokotsa ethanol le sucrose ho noa joalokaha re bontša mona. Ho feta moo, ho noa lijo ho ne ho fokotseha ka nakoana ho latela lijo tsa ho ja lijo. Ho feta moo, ho ja dijo tse phahameng kapa ts'ebetso ea tsoekere li 'nile tsa bontšoa ho fokotsa phepelo ea psychostimulant le boemo bo khethiloeng sebakeng sa likhoto [10-13]. Liphuputso tse 'maloa tse khōlō tsa ho epidemiological li boetse li bontša hore botenya ba motho hangata ha bo amane le mathata a joala kapa a sebelisoang ke lithethefatsi [45-48]. Ka lehlakoreng le leng, ho na le lithuto tse fokolang tse fanang ka bopaki ba hore lijo tsa pele tsa mafura kapa li-sucrose tsamaiso li eketsa ho noa ethanol ka likhoto [14, 15] kapa hore botenya bo amahanngoa le mathata a ho sebelisa joala bathong [49]. Tsamaiso e tloaelehileng ea ethanol e ka boela ea hlahisa matla a itseng ka tšebeliso ea lithethefatsi. Ka mohlala, tlhahiso ea ethanol e sa foleng ea pele e eketsa ethanol ho ipusa [50], empa ha e na phello ho k'hok'heine ea tsamaiso ea [51], le hoja tsamaiso e sa foleng ea ethanol kapa ea cocaine e hlahisa mekhoa e tšoanang le ea tsamaiso ea DA. Ho feta moo, mabapi le hore na boemo ba hypodopaminergic bo ama joang ho noa ethanol le ho khutlela morao, phuputso ea morao tjena e hlahlobile liphetoho tsamaisong ea DA ho pholletsa le lebelo la ho lemalla litoeba le batho, 'me le bontšitse hore ho ithiba ho khetholloa ke hypodopaminergia ea pele ho latela hyperdopaminergia nakong ea ho ikhula nako e telele, ka bobeli ea eona e ka tlatsetsang ho khutlisetsa ts'oaetso kotsing [52]. Ka lebaka leo, ho ba le mekhoa e fapaneng le ho sebelisoa ha DAergic ho amahanngoa le ho sebelisoa ha ethanol le bothata ba tšebeliso ea joala, empa kamano e nepahetseng ea lipontšo tsa DA le ho noa ethanol e ntse e sa hlaka.
Boemo ba ho eketseha ha D2R ho thibela ho ja haholo ho bakoang ke lijo
Ho eketseha ha lefu la D2R ho ka tlatsetsa ho fokolang ha phetisetso ea AIDS e hlaselang 'me e lefa hypofunction e fumanoang ka botenya bo bakoang ke ho ja. Botenya bo amahanngoa le litšenyehelo ka moputso hammoho le ho holofala maikutlong le maikutlong hangata ho boleloang ka karolo e fokotsang ho fokotsa ts'oaetso ea DA ka mokhoa o fokolang [32, 33, 53]. Ho bontšitsoe hore lijo tsa ho ja lijo tsa lijo li fokotsa maemo a mabe a DA hammoho le methapo ea metabolite ea DA ea 3,4-dihydroxyphenylacetic acid (DOPAC) le acid acid (HVA) ho NAc [5]. Ho feta moo, phuputso e 'ngoe e bontšitse hore botenya bo tloaelehileng bo hlahisitsoe li-50% tse fokolang ka tlaase ho DA ho NAc ha li bapisoa le litsamaiso [54]. Lithuto tsena tse peli li fana ka bopaki ba hore lijo tsa ho ja lijo le ho nona haholo likokoanyana tse tloaelehileng li na le likhaello tsa presynaptic ho DA ho lokolloa ho sebelisa litokisetso tsa marang-rang a NAc. Ka mohlala, ho ba le bothata bo botenya haholo ba likhoto bo ne bo fokotseha ka enzyme ea DA e bitsoang birosynthetic enzyme tyrosine hydroxylase le vesicular monoamine transporter 2 (VMAT2) e ka fokotsang ts'ebetso ea DA le ho lokolloa [54]. Leha ho le joalo, ho hlokomolohuoa tšimong ke ho kenella ha lits'ebeletso tsa 'mele VTA moo boholo ba li-neuron tsa DA li simolohang teng. Liphetho tsa morao-rao li bontša hore ho eketseha ha motlakase oa D2R ho ka tlatsetsa ho fokolang ha DAergic ho hlokometsoe ke botenya bo bakoang ke ho ja haholo. Ka hona, lipatlisiso tsa ho hlahloba mekhoa ea presynaptic mesolimbic ea NAc le VTA e ka fana ka temohisiso ka mekhoa ea neurobiological e tlatsetsang ho boima haholo.
Nahanisisa
Ho fokotsa ho fetisoa ha DA ha ho e-na le batho ba batenya haholo le likhoto li ngotsoe hantle [6, 8, 19]. Thuto ea hona joale e fana ka maikutlo a hore ho eketseha ha D2R ho itšireletsa ka VTA ho ka boela ha kenya letsoho ho fokolang ho fanoang ha DA ho fetisa lijo le moputso oa hypofunction o hlokometsoeng ka botenya. Le hoja lijo tse phahameng tsa lik'halori le lithethefatsi tsa tlhekefetso li hlahisa liphetoho tse tšoanang le ts'ebetsong ea DA tsamaiso ea meso, re bontša hore lijo tsa ho ja lijong li fokotsa ho noa ethanol ka likhoto. Ka kakaretso, ho bonahala eka lijo tsa ho ja lijo-tse bakoang ke ho lemalla lithethefatsi tsamaisong ea DA li ka tsamaisa lijo tsa ho ja lijo tsa motlakase [6], ha ho tlohela ho ja lijo tsa ho ja lijo ho fella ka ho hatelloa nako e telele ea ho noa ethanol 'me ka nakoana ho thibela ho sebelisoa ha moputso oa tlhaho (ie, sucrose le chow pellets). Liphuputso tsena li eketsa lingoliloeng tse ntseng li hōla tse bontšang hore botenya bo bakoang ke ho ja haholo le ho lemalla lithethefatsi li hlahisa li-neuroadaptations tse tšoanang ho potoloho ea potoloho. Phuputso e eketsehileng ka har'a metsoako ea Daergic ho latela mefuta e mengata ea lijo tse matla haholo kapa ho noa lithethefatsi ho ka lebisa tlhokomelo ea bohlokoa mekhoeng e tlatsetsang ho mathata ana a bophelo bo boholo.
Ho tšehetsa boitsebiso
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | 24 | 25 | 26 | 27 | 28 | 29 | 30 | 31 | 32 | 33 | 34 | 35 | 36 | 37 | 38 | 39 | 40 | 41 | 42 | 43 | 44 | 45 | 46 | 47 | 48 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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2 | ||||||||||||||||||||||||||||||||||||||||||||||||
3 | Setšoantšo sa 1A. Khalori ka beke | |||||||||||||||||||||||||||||||||||||||||||||||
4 | Khetsa feela (ID) feela | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | |||||||||||||||||||||||||||||||||
5 | Beke ea 1 | 464 | 484 | 504 | 456 | 492 | 176 | 276 | 284 | 376.4445 | 463.5555 | 438.6667 | 392 | 283.1111 | 301.7778 | |||||||||||||||||||||||||||||||||
6 | Beke ea 2 | 712 | 700 | 788 | 680 | 728 | 452 | 492 | 452 | 660.8 | 705.6 | 733.6 | 672 | 621.6 | 571.2 | |||||||||||||||||||||||||||||||||
7 | Beke ea 3 | 662.6667 | 653.3333 | 802.6667 | 634.6667 | 630 | 512 | 484 | 488 | 700 | 728 | 777 | 452.6667 | 616 | 576.3333 | |||||||||||||||||||||||||||||||||
8 | ||||||||||||||||||||||||||||||||||||||||||||||||
9 | Lijo tsa lijo tsa ho ja lijo (ID) | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | ||||||||||||||||||||||||||||
10 | Beke ea 1 | 810.11 | 783.9116 | 813.6035 | 857.5615 | 705.5117 | 780.7995 | 354.83 | 414.8343 | 354.5233 | 515.7778 | 386.4445 | 393.1111 | 466.1111 | 489.3333 | 337.5555 | 466.4445 | 398.8889 | 440.5555 | 320.2222 | ||||||||||||||||||||||||||||
11 | Beke ea 2 | 971.8041 | 1003.042 | 946.6136 | 1012.289 | 946.2327 | 926.5184 | 569.1601 | 530.6304 | 546.8109 | 788.8925 | 740.2822 | 916.6797 | 680.6889 | 857.7944 | 756.5599 | 805.8618 | 796.4995 | 834.9358 | 687.0909 | ||||||||||||||||||||||||||||
12 | Beke ea 3 | 1258.863 | 1219.169 | 1219.993 | 1210.393 | 1121.678 | 1124.869 | 631.8867 | 656.8687 | 587.3893 | 897.3823 | 882.5435 | 936.5898 | 860.3552 | 1045.424 | 864.0526 | 990.0101 | 867.4072 | 941.0391 | 893.0363 | ||||||||||||||||||||||||||||
13 | ||||||||||||||||||||||||||||||||||||||||||||||||
14 | ||||||||||||||||||||||||||||||||||||||||||||||||
15 | Setšoantšo sa 1B. Mohloli oa lik'halori (sehlopha sa lijo tsa ho ja lijo tsa motsoako oa lijo) | |||||||||||||||||||||||||||||||||||||||||||||||
16 | Li-pellets tsa chow | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | ||||||||||||||||||||||||||||
17 | Beke ea 1 | 144 | 128 | 112 | 60 | 156 | 64 | 132 | 104 | 189.7778 | 96.44444 | 59.11111 | 199.1111 | 233.3333 | 15.55556 | 208.4444 | 80.88889 | 71.55556 | 34.22222 | 116 | ||||||||||||||||||||||||||||
18 | Beke ea 2 | 320 | 268 | 292 | 224 | 284 | 148 | 76 | 188 | 243.6 | 207.2 | 243.6 | 201.6 | 366.8 | 221.2 | 324.8 | 212.8 | 182 | 201.6 | 312 | ||||||||||||||||||||||||||||
19 | Beke ea 3 | 182 | 182 | 149.3333 | 102.6667 | 196 | 184 | 68 | 204 | 207.6667 | 144.6667 | 238 | 156.3333 | 284.6667 | 163.3333 | 245 | 221.6667 | 228.6667 | 142.3333 | 261.3333 | ||||||||||||||||||||||||||||
20 | ||||||||||||||||||||||||||||||||||||||||||||||||
21 | Lijo tsa lijo tsa ho ja lijo | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | ||||||||||||||||||||||||||||
22 | Beke ea 1 | 694.11 | 639.9116 | 685.6035 | 745.5615 | 645.5117 | 624.7995 | 290.83 | 282.8343 | 250.5233 | 326 | 290 | 334 | 267 | 256 | 322 | 258 | 318 | 369 | 286 | ||||||||||||||||||||||||||||
23 | Beke ea 2 | 659.8041 | 683.0422 | 678.6136 | 720.2889 | 722.2327 | 642.5184 | 421.1601 | 454.6304 | 358.8108 | 545.2925 | 533.0823 | 673.0798 | 479.0889 | 490.9944 | 535.3599 | 481.0618 | 583.6995 | 652.9358 | 485.4909 | ||||||||||||||||||||||||||||
24 | Beke ea 3 | 997.5293 | 1037.169 | 1037.993 | 1061.059 | 1019.012 | 928.8688 | 447.8867 | 588.8687 | 383.3893 | 689.7157 | 737.8768 | 698.5898 | 704.0219 | 760.7576 | 700.7192 | 745.0101 | 645.7406 | 712.3724 | 750.7029 | ||||||||||||||||||||||||||||
25 | ||||||||||||||||||||||||||||||||||||||||||||||||
26 | Setšoantšo sa 1C. Likhalori tse tsoang ho Chow | |||||||||||||||||||||||||||||||||||||||||||||||
27 | Khetsa feela (ID) feela | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | |||||||||||||||||||||||||||||||||
28 | Beke ea 1 | 464 | 484 | 504 | 456 | 492 | 176 | 276 | 284 | 376.4445 | 463.5555 | 438.6667 | 392 | 283.1111 | 301.7778 | |||||||||||||||||||||||||||||||||
29 | Beke ea 2 | 712 | 700 | 788 | 680 | 728 | 452 | 492 | 452 | 660.8 | 705.6 | 733.6 | 672 | 621.6 | 571.2 | |||||||||||||||||||||||||||||||||
30 | Beke ea 3 | 662.6667 | 653.3333 | 802.6667 | 634.6667 | 630 | 512 | 484 | 488 | 700 | 728 | 777 | 452.6667 | 616 | 576.3333 | |||||||||||||||||||||||||||||||||
31 | ||||||||||||||||||||||||||||||||||||||||||||||||
32 | Lijo tsa lijo tsa ho ja lijo (ID) | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | ||||||||||||||||||||||||||||
33 | Beke ea 1 | 144 | 128 | 112 | 60 | 156 | 64 | 132 | 104 | 189.7778 | 96.44444 | 59.11111 | 199.1111 | 233.3333 | 15.55556 | 208.4444 | 80.88889 | 71.55556 | 34.22222 | 116 | ||||||||||||||||||||||||||||
34 | Beke ea 2 | 320 | 268 | 292 | 224 | 284 | 148 | 76 | 188 | 243.6 | 207.2 | 243.6 | 201.6 | 366.8 | 221.2 | 324.8 | 212.8 | 182 | 201.6 | 312 | ||||||||||||||||||||||||||||
35 | Beke ea 3 | 182 | 182 | 149.3333 | 102.6667 | 196 | 184 | 68 | 204 | 207.6667 | 144.6667 | 238 | 156.3333 | 284.6667 | 163.3333 | 245 | 221.6667 | 228.6667 | 142.3333 | 261.3333 | ||||||||||||||||||||||||||||
36 | ||||||||||||||||||||||||||||||||||||||||||||||||
37 | Setšoantšo sa 1D. Boima bo fumanoang ka beke (g) | |||||||||||||||||||||||||||||||||||||||||||||||
38 | Khetsa feela (ID) feela | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | |||||||||||||||||||||||||||||||||
39 | Beke ea 1 | 55 | 57 | 61 | 50 | 52 | 35 | 39 | 36 | 45.5 | 49.7 | 52.5 | 46.9 | 40.6 | 39.2 | |||||||||||||||||||||||||||||||||
40 | Beke ea 2 | 64 | 58 | 63 | 52 | 67 | 52 | 51 | 48 | 48.5 | 51.3 | 54.25 | 51.35 | 44.9 | 42.3 | |||||||||||||||||||||||||||||||||
41 | Beke ea 3 | 43 | 51 | 57 | 49 | 39 | 32 | 43 | 40 | 50.75 | 52.5 | 55.5625 | 54.6875 | 48.125 | 44.625 | |||||||||||||||||||||||||||||||||
42 | ||||||||||||||||||||||||||||||||||||||||||||||||
43 | Lijo tsa lijo tsa ho ja lijo (ID) | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | ||||||||||||||||||||||||||||
44 | Beke ea 1 | 61 | 63 | 62 | 70 | 60 | 58 | 33 | 37 | 37 | 51.8 | 42 | 53.2 | 42.7 | 55.3 | 49.7 | 47.6 | 48.3 | 49.7 | 46.2 | ||||||||||||||||||||||||||||
45 | Beke ea 2 | 67 | 72 | 70 | 69 | 59 | 59 | 52 | 58 | 59 | 58.95 | 50 | 59.55 | 50.05 | 66.7 | 57.3 | 56.15 | 58.2 | 52.55 | 55.8 | ||||||||||||||||||||||||||||
46 | Beke ea 3 | 68 | 63 | 66 | 66 | 61 | 59 | 43 | 54 | 47 | 64.3125 | 56 | 64.3125 | 55.5625 | 75.25 | 63 | 62.5625 | 65.625 | 54.6875 | 63 | ||||||||||||||||||||||||||||
47 | ||||||||||||||||||||||||||||||||||||||||||||||||
48 | Setšoantšo sa 1E. Boima ba 'mele (g) | |||||||||||||||||||||||||||||||||||||||||||||||
49 | Khetsa feela (ID) feela | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | 24 | 25 | 26 | 27 | 28 | 29 | 30 | 31 | 32 | 33 | 34 | 35 | 36 | 37 | 38 | 39 | 40 | 41 | 42 | 43 | 44 | 45 | 46 | |
50 | Ka letsatsi le | 1 | 180 | 183 | 190 | 217 | 226 | 193 | 181 | 203 | 197 | 223 | 211 | 134 | 207 | 195 | 206 | 208 | 182 | 148 | 147 | 183 | 167 | 174 | 199 | 159 | 184 | 157 | 174 | 178 | 185 | 145 | 186 | 228 | 222 | 208 | 224 | 222 | 211 | 216 | 150 | 169 | 150 | 147 | 159 | 163 | 172 | 165 |
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Lintlha tse hlakileng tsa Fig 1.
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Dintlha tsa S1. Lintlha tse hlakileng bakeng sa Setšoantšo sa 1.
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Dintlha tsa S2. Lintlha tse hlakileng bakeng sa Setšoantšo sa 2.
https://doi.org/10.1371/journal.pone.0183685.s002
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Dintlha tsa S3. Lintlha tse hlakileng bakeng sa Setšoantšo sa 3.
https://doi.org/10.1371/journal.pone.0183685.s003
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Dintlha tsa S4. Lintlha tse hlakileng bakeng sa Setšoantšo sa 4.
https://doi.org/10.1371/journal.pone.0183685.s004
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Dintlha tsa S5. Lintlha tse hlakileng bakeng sa Setšoantšo sa 5.
https://doi.org/10.1371/journal.pone.0183685.s005
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lumela hore baa fokola
Re rata ho lumela Jorge Tovar Diaz, Regina Mangieri, Nhi Le, Jeremia Ling, le Trevor Hadley ka thuso ea bona ea theknoloji. Hape re rata ho leboha Michela Marinelli bakeng sa lipuisano tsa bohlokoa tsa saense le Christopher Mazzone bakeng sa thuso ea ho fetola mongolo o ngotsoeng ka letsoho.
References
1. Volkow ND, Wang GJ, Fowler JS, Tomasi D, R. Baler. Moputso oa lijo le lithethefatsi: lipotoloho tse qalang ka botenya ba motho le ho lemala. Top Behav Neurosci ea Curr. 2012; 11: 1-24. Epub 2011 / 10 / 22. pmid: 22016109.
2. Volkow ND, Wang GJ, Fowler JS, Logan J, Hitzemann R, Ding YS, le al. Ho fokotseha ka li-receptor tsa dopamine empa eseng ka li-dopamine tse fetisang lithethefatsi tse tahiloeng. Alcohol Clinic Exp Res. 1996; 20 (9): 1594-8. Epub 1996 / 12 / 01. pmid: 8986209.
3. Moore RJ, Vinsant SL, Nader MA, Porrino LJ, Friedman DP. Phello ea k'hok'heine ea ho itšireletsa ka li-dopamine D2 receptors ho rhesus monkeys. Synapse. 1998; 30 (1): 88-96. Epub 1998 / 08 / 15. pmid: 9704885.
4. Rossetti ZL, Hmaidan Y, Gessa GL. Tšoao ea ho thibela ho lokoloha ha dopamine ea mesosombic release: e leng ntho e tloaelehileng ea ethanol, morphine, cocaine le amphetamine ho itokolla ho likhoto. Eur J Pharmacol. 1992; 221 (2-3): 227-34. Epub 1992 / 10 / 20. pmid: 1426002.
5. Geiger BM, Haburcak M, Avena NM, Moyer MC, Hoebel BG, Pothos EN. Ho senyeheloa ha maikutlo a monopolisi a dopamine ho fokolloa ke litekanyetso tsa lithethefatsi. Khopolo-taba. 2009; 159 (4): 1193-9. Epub 2009 / 05 / 05. pmid: 19409204;
6. Johnson PM, Kenny PJ. Dopamine D2 receptors ka ho lemalla ho lemalla ho lemala le ho qobella ho ja likhoto tse ngata. Nat Neurosci. 2010; 13 (5): 635-41. Epub 2010 / 03 / 30. pmid: 20348917;
7. Rada P, Bocarsly ME, Barson JR, Hoebel BG, Leibowitz SF. Ho fokotseha ho bokella dopamine linthong tsa Sprague-Dawley tse tloaelehileng ho ja lijo tse ngata tse nang le mafura. Physiol Behav. 2010; 101 (3): 394-400. Epub 2010 / 07 / 21. pmid: 20643155;
8. G. GJ, G. G. N., G. G. N., G. G. N., G. Dopamine ea boko le botenya. Lancet. 2001; 357 (9253): 354-7. Epub 2001 / 02 / 24. pmid: 11210998.
9. Stice E, Spoor S, Bohon C, Nyenyane ea DM. Likamano pakeng tsa botenya le ho arabela ka mokhoa o fokolang oa lijo li nkiloe ke TaqIA A1 allele. Saense. 2008; 322 (5900): 449-52. Epub 2008 / 10 / 18. pmid: 18927395;
10. Wellman PJ, Nation JR, Davis KW. Mathata a ho fumana k'hok'heine ea boipheliso ka likhoto tse bolokiloeng lijong tse mafura haholo. Pharmacol Biochem Behav. 2007; 88 (1): 89-93. Epub 2007 / 09 / 04. pmid: 17764729;
11. Kanarek RB, Mathes WF, Przypek J. Intake ea lijo tsa sucrose kapa mafura a fokotsa amphetamine ho noa ka likhoto. Pharmacol Biochem Behav. 1996; 54 (4): 719-23. Epub 1996 / 08 / 01. pmid: 8853195.
12. Davis JF, Tracy AL, Schurdak JD, Tschop MH, Lipton JW, Clegg DJ, et al. Ho ipapisa le maemo a phahame a mafura a mahlahahlaha a khathatsang psychostimulant moputso le mesolimbic dopamine tlhahiso ho rat. Behav Neurosci. 2008; 122 (6): 1257-63. Epub 2008 / 12 / 03. pmid: 19045945;
13. Hryhorczuk C, Florea M, Rodaros D, Poirier I, Daneault C, Des Rosiers C, et al. Dampened Mesolimbic Dopamine Function le Signaling ka Saturated empa e se Monounsaturated Dietary Lipids. Neuropsychopharmacology. 2016; 41 (3): 811-21. Epub 2015 / 07 / 15. pmid: 26171719;
14. Avena NM, Carrillo CA, Needham L, Leibowitz SF, Hoebel BG. Litoeba tse itšetlehileng ka tsoekere li bontša ho ja lijo tse matlafatsang tsa ethanol e sa tsoehang. Joala. 2004; 34 (2-3): 203-9. Epub 2005 / 05 / 21. pmid: 15902914.
15. Carrillo CA, Leibowitz SF, Karatayev O, Hoebel BG. Lijo tse ngata kapa mafura a lipids li etsa hore ethanol e je. Joala. 2004; 34 (2-3): 197-202. Epub 2005 / 05 / 21. pmid: 15902913.
16. Takase K, Tsuneoka Y, Oda S, Kuroda M, Funato H. Haholo-mafura a lijo a fepa boitšoaro bo hlephileng-, ba boiketlo ba sechaba, le bo nang le moputso oa litoeba ntle le ho nona haholo. Botenya (Silver Spring). 2016; 24 (4): 886-94. Epub 2016 / 02 / 19. pmid: 26890672.
17. Pekkanen L, Eriksson K, Sihvonen ML. Liphetoho tse entsoeng ka makhetlo ho sebelisoang ha ethanol ka boithatelo le metabolism ea ethanol phakong. Br J Nutriti. 1978; 40 (1): 103-13. Epub 1978 / 07 / 01. pmid: 666993.
18. Ogden CL, Carroll MD, Kit BK, Flegal KM. Ho ata ha bongoana le botenya ba motho e moholo United States, 2011-2012. JAMA. 2014; 311 (8): 806-14. Epub 2014 / 02 / 27. pmid: 24570244.
19. Volkow ND, RA ea bohlale. Ho lemalla lithethefatsi ho ka re thusa joang ho utloisisa botenya? Nat Neurosci. 2005; 8 (5): 555-60. Epub 2005 / 04 / 28. pmid: 15856062.
20. Wang YC, Bleich SN, Gortmaker SL. Ho eketsa monehelo oa lik'halori ho tsoa ho lino tse tsoekere tse tsoekere le 100% lero la litholoana har'a bana ba Amerika le bacha, 1988-2004. Lingaka. 2008; 121 (6): e1604-14. Epub 2008 / 06 / 04. pmid: 18519465.
21. Lustig RH, Schmidt LA, CD ea Brindis. Bophelo bo botle ba sechaba: 'Nete e chefo ka tsoekere. Tlhaho. 2012; 482 (7383): 27-9. Epub 2012 / 02 / 03. pmid: 22297952.
22. Vikraman S, CD ea Fryar, Ogden CL. Tlhaloso ea Caloric Lijong Tse Tloaelehileng Har'a Bana le Bacha ba United States, 2011-2012. NCHS Data Short. 2015; (213): 1-8. pmid: 26375457.
23. Heyne A, Kiesselbach C, Sahun I, McDonald J, Gaiffi M, Dierssen M, le al. Mohlala oa liphoofolo oa boitšoaro bo qobelloang ba lijo. Ho lemalla Moferefere. 2009; 14 (4): 373-83. Epub 2009 / 09 / 11. pmid: 19740365.
24. Pucak ML, Grace AA. Bopaki bo neng bo sebelisana le bahanyetsi ba dopamine bo etsa hore dopamine neuron e thuse haholo-holo ka ho thibela li-autoreceptor tsa somatodendritic. J Pharmacol Exp Ther. 1994; 271 (3): 1181-92. Epub 1994 / 12 / 01. pmid: 7996424.
25. White FJ, Wang Le. A10 dopamine neurons: karolo ea li-autoreceptors ho khethollang tekanyo ea ho thunya le kutloisiso ho li-agonists. Bophelo Sci. 1984; 34 (12): 1161-70. Epub 1984 / 03 / 19. pmid: 6708722.
26. Lacey MG, Mercuri NB, North RA. Dopamine e sebetsana le li-receptor tsa D2 ho eketsa mokhoa oa potassium oa ho itšoara ka mahlakoreng a rat e ngata ea nigra zona compacta. J Physiol. 1987; 392: 397-416. Epub 1987 / 11 / 01. pmid: 2451725;
27. Beckstead MJ, Ntate-moholo DK, Wickman K, Williams JT. Ho lokolloa ha dopamine e tloaelehileng ho etsa hore ho be le letšoao le thibelang ho fetela ka morao ka har'a methapo ea dopamine neurons. Neuron. 2004; 42 (6): 939-46. Epub 2004 / 06 / 23. pmid: 15207238.
28. Luscher C, Slesinger PA. Mesebetsi e hlahelletseng bakeng sa litebelisoa tsa potoloamo (GIRK) tse lokisoang ka hare ka hare ho G-G ka ho kula le mafu. Nat Rev Neurosci. 2010; 11 (5): 301-15. Epub 2010 / 04 / 15. pmid: 20389305;
29. Perra S, Clements MA, Bernier BE, Morikawa H. Ka vivo ethanol boiphihlelo bo eketsa D (2) autoinhibition sebakeng sa ventral tegmental. Neuropsychopharmacology. 2011; 36 (5): 993-1002. Epub 2011 / 01 / 21. pmid: 21248720;
30. Gantz SC, Robinson BG, DC Buck, Bunzow JR, Neve RL, Williams JT, le al. Tlhophiso e fapaneng ea dopamine D2S le D2L ho itšireletsa ka calcium. Elife. 2015; 4. Epub 2015 / 08 / 27. pmid: 26308580;
31. Rolls BJ, Rowe EA, Turner RC. Ho ba le botenya bo tsoelang pele ho likhoto ho latela nako ea ho sebelisoa ha lijo tse tsoakiloeng tse matla. J Physiol. 1980; 298: 415-27. Epub 1980 / 01 / 01. pmid: 6987379;
32. Wang GJ, Volkow ND, Fowler JS. Karolo ea dopamine e susumetsang lijo ho batho: sepheo sa botenya. Litsebi tsa Opin ther Ther. 2002; 6 (5): 601-9. Epub 2002 / 10 / 22. pmid: 12387683.
33. Davis C, Strachan S, Berkson M. Senseitivity ho tla putsa: sepheo sa ho ja haholo le ho feta tekano. Takatso ea lijo. 2004; 42 (2): 131-8. Epub 2004 / 03 / 11. pmid: 15010176.
34. Blum K, Thanos PK, MS Gold. Dopamine le glucose, botenya, le lefu la khaello ea mali. Front Psychol. 2014; 5: 919. Epub 2014 / 10 / 04. pmid: 25278909;
35. Sharpe AL, Varela E, Bettinger L, Beckstead MJ. Methamphetamine ho iponahatsa ka litoeba ho fokotseha maqhubu a GIRK a nang le moeli meleng ea dopamine neurons. Int J Neuropsychopharmacol. 2015; 18 (5). Epub 2014 / 12 / 19. pmid: 25522412;
36. Carroll ME, France CP, Meisch RA. Ho amoheloa ha lijo ho eketsa lithethefatsi ka molomo le ka hare ho likokoanyana. Saense. 1979; 205 (4403): 319-21. Epub 1979 / 07 / 20. pmid: 36665
37. Middaugh LD, Kelley BM, Bandy AL, McGroarty KK. Tšebeliso ea Ethanol ke C57BL / 6 litoeba: tšusumetso ea mefuta e sa tšoaneng ea tekano le tekano. Joala. 1999; 17 (3): 175-83. Epub 1999 / 05 / 07. pmid: 10231165.
38. Lekala SY, Goertz RB, Sharpe AL, Pierce J, Roy S, Ko D, et al. Thibelo ea lijo e eketsa ho phatloha ha li-glutamate ho fumanoa ke li-neurons tse fokolisitsoeng. J Neurosci. 2013; 33 (34): 13861-72. Epub 2013 / 08 / 24. pmid: 23966705;
39. Koyama S, Mori M, Kanamaru S, Sazawa T, Miyazaki A, Terai H, et al. Botenya bo thibela tšireletso ea D2 e thibelang ho itšireletsa ka metering ea sebaka sa putative ventral tegmental dopaminergic neurons. Physiol Rep. 2014; 2 (5): e12004. Epub 2014 / 05 / 06. pmid: 24793981;
40. Fulton S, Pissios P, Manchon RP, Stiles L, Frank L, Pothos EN, et al. Leptin molao oa tsamaiso ea dopamine tsela. Neuron. 2006; 51 (6): 811-22. Epub 2006 / 09 / 20. pmid: 16982425.
41. Labouebe G, Liu S, Dias C, Zou H, Wong JC, Karunakaran S, et al. Insulin e kenyelletsa ho tepella maikutlo nako e telele ea ventral tegmental sebakeng sa dopamine neurons ka endocannabinoids. Nat Neurosci. 2013; 16 (3): 300-8. Epub 2013 / 01 / 29. pmid: 23354329;
42. Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, et al. Ghrelin e tsamaisa mosebetsi le synaptic entries mokhatlo o hlophisitsoeng oa midbrain dopamine neurons ha a ntse a khothalletsa takatso ea lijo. J Clin 2006; 116 (12): 3229-39. Epub 2006 / 10 / 25. pmid: 17060947;
43. Koob GF, Volkow ND. Meriana ea methapo ea meriana. Neuropsychopharmacology. 2010; 35 (1): 217-38. Epub 2009 / 08 / 28. pmid: 19710631;
44. Diana M. The dopamine hypothesis ea ho lemalla lithethefatsi le matla a eona a ho phekola kalafo. Front Psychiatry. 2011; 2: 64. Epub 2011 / 12 / 07. pmid: 22144966;
45. Pickering RP, Grant BF, Chou SP, Compton WM. Na ho feta boima bo botle, botenya le botenya bo feteletseng bo amanang le lefu la kelello? Liphello tse hlahang phuputsong ea naha ea ho hlahlojoa ke mafu le maemo a amanang. J Clinic Psychiatry. 2007; 68 (7): 998-1009. Epub 2007 / 08 / 10. pmid: 17685734.
46. Simon GE, Ho Korff M, Saunders K, Miglioretti DL, Crane PK, van Belle G, et al. Bonngoe pakeng tsa botenya le mafu a kelello ho batho ba baholo ba Amerika. Arch Gen Psychiatry. 2006; 63 (7): 824-30. Epub 2006 / 07 / 05. 63 / 7 / 824 pmid: 16818872;
47. Scott KM, McGee MA, Wells JE, Oakley Mohapatra MA. Botenya le mathata a kelello ho batho ba baholo ka kakaretso. J Psychosom Res. 2008; 64 (1): 97-105. Epub 2007 / 12 / 26. pmid: 18158005.
48. Scott KM, Bruffaerts R, Simon GE, Alonso J, Angermeyer M, de Girolamo G, et al. Botenya le mafu a kelello ho batho bohle: liphello tsa lipatlisiso tsa bophelo bo botle ba kelello. Int J Obes (London). 2008; 32 (1): 192-200. Epub 2007 / 08 / 23. pmid: 17712309;
49. Barry D, Petry NM. Mekhatlo e teng pakeng tsa litekanyetso tsa boima ba 'mele le mathata a tšebeliso ea lithethefatsi a fapane le tekano: liphello tsa Phuputso ea National Epidemiologic ka Joala le Maemo a Amanang. Ho lemalla Behav. 2009; 34 (1): 51-60. Epub 2008 / 09 / 30. pmid: 18819756;
50. Roberts AJ, Heyser CJ, Cole M, Griffin P, Koob GF. Ho noa ho feteletseng ka ethanol ho latela histori ea ho itšetleha ha ethanol: setšoantšo sa phoofolo ea allostasis. Neuropsychopharmacology. 2000; 22: 581-94. pmid: 10788758
51. Fredriksson Ke, Adhikary S, Steensland P, Vendruscolo LF, Bonci A, Shaham Y, et al. Pele ho Ts'ebelloa ke Joala ha ho na Phello ea ho Ikamahanya le Cocaine le Ho Khutlela Lintlheng: Bopaki bo tsoang ho Mohlala oa Rat o sa Tšeheleng Gateway Hypothesis. Neuropsychopharmacology. 2016. Epub 2016 / 09 / 22. pmid: 27649640.
52. Hirth N, Meinhardt MW, Noori HR, Salgado H, Torres-Ramirez O, Uhrig S, et al. Bonnete ba fetola ho tsoa ho batho ba nang le tahi le likhoto bakeng sa boemo ba hyperdopaminergic nakong ea ho itokolla ka nako e telele. Proc Natl Acad Sci US A. 2016; 113 (11): 3024-9. Epub 2016 / 02 / 24. pmid: 26903621;
53. Blum K, Liu Y, Shriner R, Gold MS. Moputso oa potoloho oa dopaminergic activation o laola boitšoaro le takatso ea lithethefatsi. Curr Pharm Des. 2011; 17 (12): 1158-67. Epub 2011 / 04 / 16. pmid: 21492092.
54. Geiger BM, Behr GG, Frank LE, Caldera-Siu AD, Beinfeld MC, Kokkotou EG, et al. Bopaki ba ho fokola ha lipalesa tsa dopamine exocytosis ka likhoto tse tloaelehileng. Faseb J. 2008; 22 (8): 2740-6. Epub 2008 / 05 / 15. pmid: 18477764;
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