Mathata a mesolimbic dopamine ho ba le bothata ba ho ja lijo tse ngata haholo (2009)

Maikutlo: boithuto bo senola hore ho ja "lijo tsa ho jella" ho nona ho lebisa ho fokotseheng ha maemo a dopamine le karabelo e fosahetseng ea dopamine ho likhoto tse tloaelehileng tsa chow. Leha ho le joalo, likhoto li ntse li na le karabelo ea moputso lijong tsa ho jella. E 'ngoe ea lithuto tse ngata tse bonts'ang liphetoho tsa boko tse ts'oanang le tse lemaletseng lithethefatsi. Ho sebelisoa ha mefuta e mengata e sa tloaelehang ea meputso ea tlhaho ho ka lebisa bokhobeng.

Khopolo-taba. 2009 Apr 10; 159 (4): 1193-9. Doi: 10.1016 / j.neuroscience.2009.02.007. Epub 2009 Feb 11.

BM Geiger,a M. Haburcak,a NM Avena,b,c MC Moyer,c BG Hoebel,c 'me EN Pothosa,*

Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Khopolo-taba

Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.

Eya ho:

inahaneloang

Ho eketsa takatso ea "caloric" ho feteletseng bothateng ba ho ja ho ka tsamaisoa ke mekhoa e bohareng e laolang boitšoaro bo batlang moputso. Sisteme ea mesolimbic dopamine, le li-nucleus li bokellana ka ho khetheha, e fana ka moputso oa lijo le lithethefatsi. Re fuputse hore na botenya ba ratoa bo amana le liphetoho tsa dopaminergic neurotransication sebakeng seo. Liroto tsa Sprague-Dawley li ile tsa beoa lijong tsa mokhoa oa ho jella ka mokhoa oa ho ja bakeng sa ho khothatsa botenya kapa lijo tsa laboratori ho boloka boima bo tloaelehileng. Maemo a dopamine a extracellular a ne a lekantsoe ka Ka vivo tlhahlobo ea microdialysis. Ho lokolloa ha dopamine ka motlakase ho ne ho lekantsoe ex vivo ka likarolo tsa coronal tsa nucleus accumbens le dorsal striatum ho sebelisa real-time carbon fiber amperometry. Ho feta libeke tse 15, likhoto tse fepehileng ka lijo tsa ho jella li ile tsa nona (> 20% keketseho ea boima ba 'mele) mme tsa bonts'a maemo a tlase a li-extracellular accumbens dopamine ho feta likhoto tse tloaelehileng tsa boima (0.007 ± 0.001 vs. 0.023 ± 0.002 pmol / sampole; P<0.05). Ho lokolloa ha Dopamine ka har'a li-rats tse nang le botenya ho matlafalitsoe ke phephetso ea phepelo ea lijo, empa e ile ea lula e sa arabele lijong tsa chow tsa laboratori. Tsamaiso ea d-amphetamine (1.5 mg / kg ip) e boetse e senotse karabelo ea dopamine e fumanoeng litekong tsa monokotšoai. Liteko tse lekang motlakase o ileng oa etsa hore dopamine sign ex vivo e bokellaneng ka methapo e bonahale karabelo e fokolang ho liphoofolo tse batenya (12 vs. 25 × 106 dopamine limolek'hule ka ho hlohlona, P<0.05). Liphetho li bonts'a hore khaello ea mesolimbic dopamine neurotransmission e hokahane le botenya ba phepo. Ho lokolloa ha dopamine ho tepelletseng ho ka lebisa ho liphoofolo tse nonneng ho lefella ka ho ja lijo tse monate tsa "matšeliso", tšusumetso e hlahisitseng dopamine ha chow ea laboratori e hloleha.

Keywords: li-nucleus accumbens, striatum, fepa, boima ba 'mele, amphetamine, hyperphagia

Keketseho e potlakileng ea botenya ba ho ja lihlopheng tse tsoetseng pele indastering e bonts'a litsela tse sa tloheng lapeng tse lumellang tšebeliso e matla ea matla tse sa feleng. Potso ea bohlokoa ke hore na ke hobaneng ha liphoofolo le tsa batho ba ntse ba tsoela pele ho ja lijo tse matlafatsang, tse fumanehang habonolo ho isa boholeng ba hore ba be batenya. Ho latela pono ea khopolo ea ho iphetola ha lintho, ho ka lebelloa hore boko bo thehile mokhoa oa ho arabela meputsong ea tlhaho, joalo ka lijo. Mechine ena e bohareng e bolokiloe ho mefuta eohle e le ho netefatsa hore e phela (Kelley le Berridge, 2002) hape e ka sebelisana le potoloho ea potoloho e laolang boima ba 'mele. Ka hona, ho fumaneha ha lijo tse monate tse fumanehang habonolo ho ka lebisa ho matlafatso ea khalori le ho nona haholo hore mekhoa e khannoang homeostasis, e simolohileng ho hypothalamus, e kanna ea se ke ea hlola. Monyetla ona o kanna oa hlalosa, bonyane ka karolo e itseng, karolo ea seoa sa botenya ba ho ja.

E ikhethang har'a litsamaiso tsa neural ke mesolimbic dopamine pathways, moo ketso ea dopamine, haholo-holo li-terminals tsa li-nucleus, e tsejoang ka mekhoa ea matlafatso ea methapo. Ts'ebetso ea ts'ebetso ena e kenyelletsa maemo a phahameng a dopamine le liphetoho phetohong ea dopamine ka mor'a boits'oaro bo botle ba tlhaho ba ho fepa joaloka ho fepa (Hernandez le Hoebel, 1988; Radhakishun et al., 1988). Ntle le moo, dopamine ho nucleus accumbens (le haufi le dorsal striatum) e tsejoa e eketseha ka ho pepesehela ts'usumetso e amanang le lijo le ts'ebetso ea makoloi e amanang le ho fihlela lijo (Mogenson le Wu, 1982; Bradberry et al., 1991; Salamone et al., 1991). Ka hona, hoa utloahala ho lebella hore botenya ba lijo bo ka amahanngoa le bokhoni ba ho lokolla dopamine ba mesolimbic dopamine.

Thutong ena, re fuputse hore na ho pepesetsoa likhoto (libeke tsa 15) ho lijo tse nang le matla a mangata, tse fumanehang lijong tsa "ceterus" tse hlahisang phetoho ea li-choleopole tsa nucleus. Lijo tsena tse matlafatsoang haholo li atleha ho susumetsa ho nona ha lijo ka har'a likhoto mme li bohlokoa ka ho fetisisa nts'etsopeleng ea botenya ba motho (Sclafani le Springer, 1976). Ntle le moo, lijo tsa k'habeche li ile tsa re lumella ho khetholla lipakeng tsa lijo tse nang le mafura a mangata le nama e phahameng ea 'mele le hore na likhetho tse joalo li na le tšusumetso ea mesolimbic dopamine. Re fumane hore likhoto tsa Sprague-Dawley li nkile boholo ba lijo tsa bona tsa letsatsi le letsatsi tsa caloric ho tsoa mehloling e nang le lik'habohaedreite tse ngata 'me li bile le botenya bo feteletseng ba' mele (DIO). Ho feta moo, ba bonts'itse khatello ea maikutlo ea "basal dopamine" e tsoang maemong a bokellaneng le karabelo ea dopamine e fumanehang lijong tse tloaelehileng kapa tsamaisong ea methapo ea d-amphetamine.

MELAO EA TŠEBELETSO

Animals

Litšoelesa tsa basali tsa albino Sprague-Dawley (Taconic, Hudson, NY, USA), li ne li ts'oaroa bakeng sa boima ba 'mele ba 300 g motho ka mong ha a le likhoeli tsa 3. Liphoofolo tse tšehali li ile tsa khethoa hobane, ho fapana le likhoto tsa banna, boima ba 'mele ba basali ba li-laborator bo kopantsoeng bo tsitsa ha nako e ntse e tsamaea. Liphoofolo li ne li beoa ka tlung e le 'ngoe ka tlung e le' ngoe tlasa lebili la 12-h reverse light / lefifi (mabone ka: 6 pm, mabone a tima: 6 am). Tlas'a maemo ana ha rea ​​ka ra bona tšusumetso ea karolo ea estrous potoloho ea mesolimbic dopamine.Geiger et al., 2008). Liphoofolo tsohle li ile tsa sebelisoa ho latela litaelo tse phatlalalitsoeng tsa US National Institutes of Health (NIH) le Institutional Animal Care and Use Committee Committee (IACUC) ea Univesithi ea Tufts le Setsi sa Bongaka sa Tufts. Ho ile ha etsoa boiteko bohle ho fokotsa palo ea liphoofolo tse sebelisoang e le ho fokotsa tšebeliso ea liphoofolo le mahlomola.

Sebopeho sa lijo tsa cafeteria

Liphoofolo li ne li arotsoe ka sehlopha sa lijo tsa DIO (se hlalosoang hape e le sehlopha sa lijo tse nang le mafura a mangata ka tlase) le sehlopha sa laboratori chow-fed (sehlopha se tloaelehileng sa boima). Lihlopheng tsohle li ile tsa feptjoa ad libitum. Lijo tsa ka jareteng li kenyellelitse likarolo tsa mafura a mangata joalo ka Crisco (33% ho khutsufatsoa ha meroho, 67% Purina phofo), salami, chisi ea cheddar le botoro ea peanut; le likarolo tse nang le lik'habohaedreite tse ngata tse kang lebese le kolobisitsoeng hantle (mofuta oa Magnolia o kopaneng le metsi, 1: 1), li-cookies tsa chokolete, chokolete ea lebese, libanana, marshmallows le tharollo ea sucrose ea 32%. Lijo tsena tse fumanehang hantle li bontšitsoe li sebetsa hantle haholo ho khothaletsong botenya ba lijo makotong le ho etsisa kholo ea botena ba motho (Sclafani le Springer, 1976). Karolo ka 'ngoe e ne e fumaneha ka linako tsohle' me e ne e fetoloa makhetlo a mane ka beke. Sehlopha sa Lijo tsa Dico, ntle le lijo tse fumanehang habonolo, le sona se ile sa fanoa ad libitum ho fihlella laboratori ea Purina chow. Ho supa likhetho tsa lijo, ho kenella kahare ho e 'ngoe le e' ngoe ea likarolo tsa phepelo ea lijo tsa kofi ho lekantsoe makhetlo a mabeli a 48-h nakong ea beke ea leshome le motso o mong oa lijo. Boima ba 'mele bo ne bo rekisoa hang ka beke.

Ho buuoa ka thipa

Ho buuoa ka Stereotaxic ho etsoa bekeng ea 7 ea thuto (n= 24 cafe ea Dio rats, n= 32 laboratori chow rats). Liphoofolo li ne li sa anngoe ka ketamine (60 mg / kg ip) le xylazine (10 mg / kg ip) bakeng sa ho kenngoa ha li-viratoral 10 mm tse peli, li-21 gauge tsa tšepe tse sa sebetseng tsa li-cannulas tse ikemiselitseng tikoloho ea bokapele ba mahlaseli a ka morao. Likhokahanyo tsa stereotaxic e ne e le 10 mm anterior ho zero tse khubung, 1.2 mm hamorao ho ea sinsagittal sinus le 4 mm ventral ho boemo ba lehata. Mofuta oa probe dialysis o atolositse XGHNUMX e 'ngoe ea ventral ho fihlella sebaka sa sepheo (Paxinos le Watson, 2007). Kamora ho buuoa, liphoofolo tsohle li ile tsa khutlisetsoa mekotleng ea tsona 'me tsa tsoela pele ka mokhoa oa tsona oa ho ja.

Microdialysis le ts'ebetso e phahameng ea chromatography e nang le tlhahlobo ea electrochemical (HPLC-EC)

Microdialysis e entsoe nakong ea beke ea 14 ea thuto ho etsa hore pholiso e lekaneng ho tsoa opereisheneng. Bakeng sa seboka se seng le se seng sa Microdialysis liphoofolo li ne li beoa ka bonngoe ka har'a likhokahano tsa maiketsetso 'me li-probes li ne li beoa ka har'a virnialysis cannulas 12-15 h pele sampole ea pele e bokelloa. Sebaka sa ho kenella (ka ho le letšehali le ka ho le letona) se ile sa hanyetsoa. Lipatlisiso tsa Microdialysis e ne e le tsa mofuta oa lierekisi, li entsoe sebakeng sa heno mme li bonts'itse phallo ea 10% ea li-neurochemicals ho a vitro liteko joalo ka ha ho hlalositsoe pejana (Hernandez et al., 1986). Mabaka a entsoe ka tharollo ea Ringer (142 mM NaCl, 3.9 mM KCl, 1.2 mM CaCl2, 1.0 mM MgCl2, 1.4 mM Na2HPO4, 0.3 mM NaN2PO4) ka sekhahla sa 1 ° µl / min. Dialysate e ne e bokelletsoe ka lijong tsa 40 µl tse nang le 5 µl ea li-preservative (0.1 M HCl le 100 ° µM EDTA) ho liehisa oxidation ea monoamine. Ho bokelloa ha sampole ho qalile bohareng ba potoloho e lefifi, 'me lijo tsohle li ile tsa tlosoa 3 h pele ho sampole bakeng sa liphoofolo tsohle. Sampole e ile ea bokelloa mekhahlelong ea 30-min bonyane 2 h ea basement, ea lateloa ke ente ea systemic ea d-amphetamine (1.5 mg / kg ip; Sigma, St. Louis, MO, USA). Ho tsoa sampole ka 'ngoe, 25 µl ea dialysate e ile ea kenngoa ka har'a amperometric Antec HPLC-EC system (GBC, Inc., Boston, MA, USA) e nang le 10 cm Rainin kholomo le buffer ea phosphate mobile, e arohanang le ho bona dopamine, mme dopamine metabolites dihydroxyphenylacetic acid (DOPAC) le Homovanillic acid (HVA). Litlhōrō tsa eona li ile tsa lekanngoa ebe li rekisoa. Ho beoa hoa probe ea microsalysis sebakeng sa sepheo ho netefalitsoe qetellong ea tlhahlobo ka tlhahlobo ea nalane ea nalane ea probe e latelang ho lokisa boko le paraformaldehyde.

Bakeng sa liphoofolo tse hlahisoang ka phepelo ea laboratori ea 30-min kapa phephetso ea lijo tsa k'hapete sebakeng sa d-amphetamine, lihlopha tsohle li ne li fuoe lijo bakeng sa 12 h pele ho tlhahlobo ea Microbalal ho netefatsa tšusumetso e lekaneng ea ho ja.

Letlapa la elektrophone

Borena ba makotikoti bo ile ba kenngoa ka sekhahla ka har'a sethala sa "hydrogen" se nang le mocheso oa moea o batang (aCSF) ho leica viberome ea Leica VT1000S (Leica Microsystems, Wetzlar, Jeremane), 'me sa khaoloa ka mela ea 300 µm coronal. Letamo la ho sesa le ne le na leCCF (124 mM NaCl, 2.0 mM KCl, 1.25 mM KH2PO4, 2.0 mM MgSO4, 25 mM NaHCO3, 1.0 mM CaCl2, Tsoekere ea 11 mM, pH = 7.3). Kamora hore 1 h ka melaleng ea aCSF e fetisetsoe kamoreng ea ho rekota ka ho tlatsana ha oxygenated aCSF e behiloeng ho 1 ml / min ho 37 ° C. Li-electrodes tsa Carbon fiber, 5 µm ka bophara, ka sefahleho se sa tsoa beoa li ne li kentsoe khubung ea li-nucleus accumbens kapa dorsal striatum ~ 50 µm ka selikalikoe, ka terata ea li-electrode (Ag / AgCl terata) e kentsoeng ka bateng ea aCSF le mohala oa motlakase ho + 700 mV (Axopatch 200 B, Axon Instruments Inc., Union City, CA, USA). Terata e phefumolohang, e sothehileng, e nang le li-elektrode tse hlasimollang (terata ea 0.005 ho: MS 303 / 3, Plastics One, Inc., Roanoke, VA, USA) e kentsoe kahare ho 100-200 them ea li-electrode tsa carbon fiber. Khopotso e lulang e le teng ea monophasic ea hona joale ea 2 ms ho + 500 deliveredA e fanoe ke Isoflex activus exclusive (AMPI, Inc., Jerusalem, Israel) e hlohlellelitsoeng ke mohlahlami ea lulang a le teng (Model S88; Grass Technologies, West Warwick, RI, USA) . Karabelo ea electrode ea amperometric (change in baseline) e ile ea hlahlojoa le ho hlakisoa ke software ea Superscope (GW Instruments, Inc., Somerville, MA, USA). Li-Electrodes li ne li lekantsoe pele le kamora ts'ebeliso ka li-voltammogram tse tlatsitsoeng ka morao (maqhubu a mahlano a sebelisitsoe mme a kenyellelitsoe, 300 V / s, −400 ho + 1000 mV, ho rekota bohareng le bohareng ka 10 µM ​​dopamine). Lithakhisa tsa Amperometric li ile tsa khetholloa e le liketsahalo tse kholo ho feta 3.5 × lerata la rms la motheo. Bolelele ba ketsahalo e ne e le nako lipakeng tsa (a) motheo oa mantlha o tlohang mohloling oa motheo ho fihla ntlheng ea pele o neng o feta cutoff le (b) ntlha ea data e latelang kamolimo e kholo e ngolisitseng boleng ba ≤0 pA. Bophahamo bo phahameng (i, max) ea ketsahalo e ne e le boleng bo phahameng ka ho fetelletseng ketsahalo eo. Ho tseba palo ea limolek'hule tsohle (N) e lokollotsoe, tefo e felletseng ea ketsahalo lipakeng tsa methapo ea motheo e thehiloe, le palo ea limolek'hule tse hakantsoeng ke kamano N= Q /nF, Q ke bokae, n palo ea lielektrone tse fanoeng ka molek'hule ka ngoe, mme F e lula e le joalo Faraday (96,485 C ka ho lekana). Likhakanyo li ne li thehiloe khopolong ea lielektrone tse peli tse neelitsoeng ka molek'hule e le 'ngoe ea oxidule ea dopamine (Ciolkowski et al., 1994).

Li-micropunches

Cafeteria DIO kapa likhoto tsa laboratori tse fepa-holo (n= 11 / group) li ile tsa khothatsoa joalo ka ha ho ile ha etsoa liteko tsa nakong e fetileng 'me likhakanyo tsa bophara ba 1 limilimithara tsa dorsal striatum le li-bokellase tsa nucleus tsa nkuoa ho tsoa linthong tsa boko tsa 300 µm. Li-punches li ile tsa pepesetsoa tharollo ea 40 mM KCl ea 3 min ho khothaletsa ho lokolloa ha dopamine. Mefuta ea dopamine ea extracellular e ile ea lekanngoa ka mokhoa oa HPLC o hlalositsoeng ka holimo.

Tlhahlobo ea lintlha

ANOVA ea mekhahlelo e 'meli (nako ea sehlopha) e nang le mehato e phetoang le tlhahlobo ea poso ea Fisher joalo ka ha ho loketse e ile ea sebelisoa bakeng sa tlhahlobo ea data ea microdialysis. ANOVA ea tsela e le 'ngoe e ne e sebelisoa bakeng sa lits'oants'o tsohle tse ling. Bakeng sa liteko tsa silika, liphetho tse tsoang ho tse matla tse hlano tse fapaneng leqeleng le le leng li ile tsa kenyelletsoa ka leqeka le leng pele ANOVA e tsamaisoa. Liphetho li hlahisoa e le phoso e tloaelehileng ea "error phoso" (SEM).

LIPOTSO

Likhoto tsa lijo tse nang le mafura a mangata li rata lijo tse matlafatsang haholo

Likhoto tsa Cafeteria DIO li bonts'itse khetho e matla bakeng sa lebese le monate (74.4 ± 6.4 g; 241 ± 21 kcal) le 32% sucrose solution (31.4 ± 4.1 g; 40 ± 5 kcal) (Feiga. 1A, B, F(9,127) = 116.9854, P<0.01). Ntle le moo, liphoofolo tsena li jele tlase haholo ho Purina chow (5.66 ± 1.02 g) ha li bapisoa le liphoofolo tse fepehileng tsa chow tsa laboratori (54.7 ± 2.3 g; F(1,27) = 419.681, P<0.01). Kamora libeke tse 14 lijong tsa ho jella, likhoto li ile tsa fumana 53.7% ea boima ba 'mele ba bona ba pele ho isa boima ba ho qetela ba 444.9 ± 19.0 g. Kamora nako e ts'oanang, likhoto tsa chow ea laboratori li ile tsa fihlela boima ba ho qetela ba 344.0 ± 10.8 (Setšoantšo sa 2A).

Feie. 1 

Liphetho tsa motsoako oa cafeteria lijong tsa litoeba. Karolelano ea tšebeliso ea likarolo tsa phepelo ea k'hafeine ka har'a ligrama (A) le kcal (B) ka makhetlo a mabeli a 48-h nakong ea beke 11 ea mokhoa oa ho ja o bonts'a khetho ea lebese le monate le tharollo ea sucrose (bolela ± SEM; ...
Feie. 2 

Basal, amphetamine- le laboratori chow lijo tse phephetsang li-dopamine li fokotsehile maemong a lijo tsa litheko tsa "feta". (A) Boima ba 'mele ba litoro tsa Deterone ka nako ea beke ea 14 e ne e le matla haholo ho feta khabong ea laboratori ...

Lirosa tsa lijo tse nang le phepo e ntle li na le dopamine e tlase ebile li fokolitse tokollo ea dopamine ea amphetamine

Bekeng ea 14 ea boithuto, likhoto tsa Dio tsa cafeteria li ile tsa bonts'a maemo a tlase a kantle ho extracellular dopamine ho li-bokellase tsa nucleus, ha li bapisoa le li-rats tsa chow-fed (RNUMX ± 0.007 pmols / 0.001 µL sampuli, 25 µL mohlala, ka ho latellana Setšoantšo sa 2B, F(1,19) = 11.205; P<0.01), joalo ka ha e lekantsoe ke Ka vivo microsalysis. Maemo a mantlha a metabolite ea dopamine, DOPAC le HVA, le tsona li fumanoe li le tlase haholo ka har'a li-ronal tsa Dio. Maemo a DOPAC ka jareteng ea Dio tsa kofi e ne e le 3.13 ± 0.42 vs. 8.53 ± 0.56 pmol in laboratori chow-fed rats (F(1,10) = 14.727, P<0.01). Methati ea HVA e ne e le 1.0 ± 0.28 vs. 4.28 ± 0.33 pmol ka tatellano (F(1,20) = 6.931, P<0.05). Kamora ho theha motheo o tsitsitseng oa dopamine, likhoto li ile tsa fuoa ente ea 1.5 mg / kg ip ea amphetamine. Ho lokolloa ka botlalo ha maemo a dopamine a neng a hlohlellelitsoe ho ne ho le tlase haholo litulong tsa ho jella tsa DIO ha ho bapisoa le liphoofolo tse fepehileng ka laboratoriSetšoantšo sa 2B, F(9,162) = 2.659, P

Likhoto tsa lijo tse nang le phepo e nepahetseng li lokolla dopamine ka har'a nucleus ea lijo ha li ja lijo tse fumanehang habonolo, eseng laboratori e hlakileng.

Setšoantšo sa 2D e bonts'a hore maemo a dopamine ea extracellular dopamine lijong tsa Dio ha a ka a eketseha ka mokhoa o hlakileng ha a arabela lijong tsa laboratori chow. Liphoofolo li jele ka bongata ba 1.3 ± 0.4 g ea chow e fetang 30 min. Leha ho le joalo, ha se ka tlase sa liphoofolo tsena (n= 8) e ile ea fuoa phepelo ea lijo tsa jarete bakeng sa 30 min, dopamine e ile ea eketsa 19.3% ho tloha 0.027 ± 0.003 ho 0.033 ± 0.004 pmols / 25 µL sampuliF(11,187) = 8.757, P<0.05). Methati ea DOPAC le eona e eketsehile ka 17.13% ± 6.14%. Ka lehlakoreng le leng, maemo a dopamine liphoofolong tse fepetsoeng ka li-laboratory a eketsehile ka 51.10% ± 17.31% (F(7,119) = 3.902, P<0.05) 1 h kamora lijo tsa chow (liphoofolo li jele ka karolelano ea 5.7 ± 0.8 g, haholo ho feta liphoofolo tsa DIO; F(1,33) = 26.459, P<0.01). Leha ho le joalo, ha re lebelle hore phepelo e tlase ea lijo tsa liphoofolo tsa DIO ke sesosa se tobileng sa khaello ea tokollo ea dopamine liphoofolong tsena kaha ho tlalehoa hore ho ja lijo tse tlase ho 0.6 g ho hlohlelletsa ho lokolloa ha dopamine ka har'a li-nucleus tsa likhoto (Martel le Fantino, 1996). Ntle le moo, liphuputso tse ling li bonts'itse hore phapang ea palo ea dopamine e lokollotsoeng ha e hlile e amana le palo ea lijo tse teng, empa e ka ameha le tse ling tse susumetsang tse kang boemo ba phoofolo, botsitso le litlamorao tse ncha tsa lijo tse hlahisitsoeng. (Hoebel et al., 2007). Lijo tsa k'hapete ha lia ka tsa fanoa e le phephetso ho liphoofolo tse fepeloang laboratori hobane ho ne ho lebelletsoe ho hlahisa lits'oants'o tse ncha tse ka ferekanyang ho bapisoa le liphoofolo tsa Dio tsa cafeteria.

Ho lokolloa ha dopamine ka motlakase ho kenngoa ka har'a likotoana tsa boko bo boholo ho tsoa ho likhoto

Setšoantšo sa 3A e bonts'a moemeli oa "amestometric" ho latela li-ligus tsa "nucleus" tse bokellaneng likhetla tsa litoeba tse tloaelehileng tsa likhapha tsa lijo.n= Litšusumetso tsa 30 ka likhalase tse supileng li ts'oaroa ke 24 lits'oants'o tse hlano ka tatellano). Likhoto tsa Cafeteria DIO li ne li ntšitse tlhahiso ea dopamine ka motlakase ho feta likhoto tsa laboratori tse pakiloeng (12 × 106± 4 × 106 vs 25 × 106± 6 × 106 limolek'hule; Setšoantšo sa 3B, F(1,52) = 2.1428, P<0.05). Phapang ena ea tokollo ea dopamine e hlahisitsoeng e bonts'a ho fokotseha ha bophahamo ba ketsahalo (5.16 ± 1.10 pA lijong tsa ho jella tsa DIO likhakanyo le 7.06 ± 0.80 pA ho likhoto tse fepehileng tsa laboratori; Setšoantšo sa 3C, F(1,52) = 2.4472, P<0.05) le bophara (2.45 ± 0.73 s sebakeng sa ho jella likhoto tsa DIO khahlanong le 4.43 ± 0.70 s ho likhoto tse fepehileng ka laboratori, Setšoantšo sa 3D, F(1,52) = 3.851, P

Feie. 3 

Ho lokolloa ha dopamine ho tsoa ho li-nucleus tse bokellaneng lipeong tsa boko (A) Lits'oaetso tsa moemeli ho tsoa ho li-acute tsa coronal nucleus li bokellana ka mefuta ea liphoofolo tse fepiloeng (holimo; n= Ts'usumetso ea 30 ka linoko tse supileng) le liphoofolo tsa Dico tsa cafeteria (ka tlase; n= Liphetoho tsa 24 ...

Feie. 4 e bonts'a mekhoa e ts'oanang e neng e le teng litekong tsa litheko tsa litonki tsa phepo e nepahetseng. Matšoao a moemeli a tsoang laboratori ea chow-feed (n= Ts'usumetso ea 31 ka linoko tse supileng) le cafeteria ea Dio (n= Litšusumetso tsa 15 ka mela e mene) lihlopha li bonts'oa Setšoantšo sa 4A. Ho lokolloa ha dopamine ka motlakase ho tsoa striatum e ne e le 0.8 × 106± 0.1 × 106 lijong tsa Dio rats vs 44 × 106± 11 × 106 limolek'hule (Setšoantšo sa 4B, F(1,45) = 6.0546, P<0.01) liphoofolong tse fepetsoeng ka li-laboratory. Hape sena se bonts'a phokotso ea bophahamo ba ketsahalo ka bobeli (2.77 ± 0.42 vs. 9.20 ± 1.88 pA; F(1,45) = 7.8468, P<0.01) le bophara (0.22 ± 0.03 vs. 5.90 ± 0.98 s; F(1,45) = 17.2823, P<= 0.01) sehlopheng sa ho jella sa DIO (Feiga. 4C, 4D).

Feie. 4 

Ho tsoa dopamine ho tsoa ho dorsal striatum likomong tsa boko. (A) Boemeli bo tsoa linthong tse bobebe tse tsoang ho liphoofolo tse fepehileng hantle (holimo; n= Ts'usumetso ea 31 ka linoko tse supileng) le liphoofolo tsa Dico tsa cafeteria (ka tlase; n= Ts'usumetso ea 15 ho ...

Ho lokolloa ha dopamine ea potasiamo e matlafalitsoeng ka har'a micropunches ea lithane ho fokotseha ho li-bokellase tsa nucleus le striatum ea likhoto tse kholo tsa lijo

Mefuta ea dopamine ea extracellular dopamine e latelang kameho ea KCl e lekantsoe ke HPLC-EC mme e bonts'itsoe Feie. 5. Mefuta ea dopamine ea extracellular e ne e le 0.16 ± 0.08 pmol / sampole ho li-micropunches tsa liphoofolo tse batona haholo (n= 10 micropunches) ha e bapisoa le 0.65 ± 0.23 pmol / sampole ho micropunches ho tsoa ho liphoofolo tse laoloang (n= 11 micropunches; Setšoantšo sa 5A; F(1,19) = 4.1911, P<0.01). Methati ea extracellular dopamine e ne e le 5.9 ± 1.7 pmol / sampole ho li-micropunches tsa striatal tse tsoang ho batenya (n= 8 micropunches) likhoto le 11.3 ± 1.9 pmol / sampole sebakeng se le seng ho tsoa taolong (n= 11 micropunches) likhoto (Setšoantšo sa 5B; F(1,17) = 7.5064, P

Feie. 5 

Maemo a dopamine ea extracellular ho tsoa ho li-micropunches tsa lithane tsa potasiamo. Palo ea dopamine e lokollotsoeng ho (A) li-nucleus accumbens (n= 11 micropunches ho tsoa sehlopheng ka seng) le (B) dorsal striatum (n= 8 micropunches e tsoang ho feta le n= 11 micropunches ho tsoa ho li-control) ...

TŠOHLOA

Thutong ena, likhoto li ile tsa nona ho feta tekano ka lebaka la ho ja lijo tsa k'habeche ka ho rata lijo tse nang le lik'habohaedreite tse ngata. Boemong ba bona ba boima bo fetisisang, ba ne ba e-na le dopamine e tlase ea basal extracellular dopamine hammoho le dopamine e matlafalitsoeng kapa amphetamine e matlafalitsoeng ka har'a li-nucleus accumbens. Lithutong tse sebelisang lithethefatsi tsa tlhekefetso, liphoofolo li tla sebetsa ho boloka maemo a dopamine ka har'a li-nucleus a bokellaneng ka holimo ho boemo bo itseng (Wise et al., 1995a,b; Ranaldi et al., 1999). Thutong ea hona joale, "ntho" e hlekefelitsoeng ke lijo tse fumanehang habonolo, ka hona, "dopamine" e tsoang kantle ho extracellular dopamine e lebisa ts'ebeliso e eketsehileng ea lijo tse fumanehang habonolo.

Likhoto tsa Obese li boetse li bonts'a litekanyetso tsa dopamine tsa motlakase ka methating ea boko le lipilisi tse matlafatsoang tse nang le potasiamo ho li-micropunches tsa tishu ho tsoa ho li-nucleus accumbens le dorsal striatum. Khetla e ka sehloohong ea presynaptic ho dopamine exocytosis, ka hona e bonahala ka botenya ba ho ja kaha ho tepella maikutlo ho lokolloang dopamine ho teng Ka vivo, ka likotoana tsa kelello tse bobebe le tse fumanehang bokong le linthong tse bobebe tse tsoang liphoofolong tse jang lijo tse nang le mafura a mangata. Re bone phello e ts'oanang mohlaleng oa liphatsa tsa lefutso oa botena. Mohlaleng ona, mRNA le polelo ea liprotheine ea li-dopamine synthesis le exocytosis ho kenyelletsa tyrosine hydroxylase le neuronal vesicular monoamine transporter (VMAT2) li fokotsehile sebakeng sa "ventral tegmental" (VTA) dopamine neurons ea liphoofolo tse lemalloang ke botenya.Geiger et al., 2008). Sebaka se seng se ka 'nang sa etsahala sa phetoho ea pele ho synaptic ke plasma membrane dopamine dupamine reuptake transporter, DAT. Lithuto tsa elektroniki tsa lesela li re lumella ho khetholla lipakeng tsa phapang ea dopamine le phallo ea kinetics. Phapano ea bophara ba spike e bonts'a ka molao-motheo oa hore liphoofolo tse jang lijo tse fetang tekano li ka 'na tsa se fuoe tokollo e fokolang empa hape le liphetoho tsa ho khutlisoa ka lebaka la liphapang tsa libaka tsa transporter tse sebetsang tsa membrane ea plasma. Ho mafura a Zucker (fa / fa) likhoto, litekanyetso tsa mRNA tse eketsehileng tsa transporter ea DAT li tlalehiloe ho VTA (Figlewicz et al., 1998). Monyetla oa ho hlakisoa ha dopamine o lumellana le lets'oao la "dopamine" le fokotsehileng le tsoang liphatseng tsa DIO thutong ea hona joale.

Re lokela ho hlokomela hore bokhoni ba ho imolla dopamine ba amphetamine bo ne bo sa fumanehe liphoofolong tse tlotsitsoeng (ho latela phetoho ea liperesente) mme sena se ka "rera" hammoho le maemo a tlase a dopamine ho susumetsa liphoofolo tse tona hore li fuoe tšusumetso ea dopamine. Amphetamine ke motheo o fokolang o tlohelang dopamine ho tloha li-vesicles ho ea cytosol mme o lebisa keketseho ea dopamine ea extracellular ka lipalangoang tse khutlisetsang morao (Sulzer le Rayport, 1990). Maemong a haelloang haholo ke matangoana a dopamine vesicular, joalo ka mohlala oa sephooko se holofetseng sa VMAT2, ente ea amphetamine butle-butle e tsosa motsoako o mocha oa dopamine ho cytosol (Fon et al., 1997). Keketseho e fokotsang ea nakoana ea amphetamine, e ka hlalosang keketseho ea nakoana ea phetoho ea liperesente tsa liphoofolo tse tlotsitsoeng ka bongata bo hlokometsoeng linthong tse tloaelehileng tsa boima mme e ka kenya letsoho ho ts'oaneleheng ha liphoofolo tse tlisoang ke lefu la dopamine ho lokolla sepheo hammoho le extracellular e tlase. maemo a dopamine ka hara li-accumbens.

Mekhoa e ka kopanyang liphoso tsa dopamine tsa presynaptic dopamine e ka ba tsa mofuta oa lijo tseo e li ratang joang? Khokahano lipakeng tsa khetho ea lijo le li-dopamine tsa nyutlelie e bonts'oa ka mokhoa o hlakileng karabelong e sa nepahalang ea liphoofolo tse jang nama ho feta empa li sa je lijo tse matlafatsang. Liphumano tsa rona li tlatsana le mosebetsi oa morao-rao o bonts'ang hore dopamine D1-mofuta oa li-receptor (d1) o ntlafalitse khetho ea likhoto bakeng sa lijo tse fumanehang habonolo (Cooper le Al-Naser, 2006). Ntle le moo, li-dopamine tsa nucleus li bokelloa ka har'a likhoto tse koetliselitsoeng ho itlopa joala ka sucrose (Avena et al., 2008), ho ts'ehetsa ho nka karolo ha dopamine e bohareng ho khethoeng ha lijo tse fumanehang habonolo tse nang le lik'habohaedreite. Re bontšitse bofokoli bo bohareng ba dopamine bo tlalehiloeng thutong ea hona joale mehlaleng e meng ea botena, ho kenyeletsa le ob / ob leptin e haellang ka lebaka la ho fokola hoa mmele le lenane la tšenyo e bakoang ke botenya (Fulton et al., 2006; Geiger et al., 2008). Kahoo, lets'oao le le leng le ka kopanyang tšebeliso ea lijo tse fumanehang habonolo le tlhahiso ea dopamine e ka ba leptin. Ho batho ba nang le bofokoli ba tlhaho ea leptin, ho khutlisetsa leptin ho fokotsa hyperphagia ea bona mme ho fetola ts'ebetso ea bona ea "ventral striatum" mabapi le pono ea lijo tse fumanehang habonolo (Farooqi et al., 2007). Litekong ho boetse ho bontšitsoe hore leptin e tla fokotsa ho itaola (Figlewicz et al., 2006, 2007). Ho kenyellelitsoe lintho tse ling tse kenyang li-orexigenic tse kang ghrelin le orexin hore li kenya letsoho ts'ebetsong ea sisteme ea midbrain dopamine (Rada et al., 1998; Helm et al., 2003; Abizaid et al., 2006; Narita et al., 2006). E ka ba ho khahlisang ho tsoela pele ho hlahloba hore na ho chencha liphoofolo tse jang mafura sebakeng sa laboratori se tloaelehileng ho ka boloka litakatso tsa 'ona tsa lijo tse fumanehang habonolo le karabelo e amanang le dopamine e ikemetseng ntle le liphetoho tse lebelletsoeng ho leptin, ghrelin kapa orexin le matšoao a mang e amanang le taolo ea takatso ea lijo.

QETELLO

Qetellong, sephetho thutong ena se bonts'a hore sisteme ea mesolimbic dopamine e bapala karolo ea bohlokoa ho ratang lijo tse nang le matla a mangata, hyperphagia le ho nona haholo. Li-bokellase tsa "li-nucleus" le "dorsal striatum dopaminergic neurotransmission" li sithabetsoa ke likhoto tsa phepo e nepahetseng. Liphoofolo li ka khutlisa maemo a dopamine ka nakoana ka ho ja lijo tse matlafatsang tse matla haholo. Liphetho tsena li fana ka maikutlo a hore ho khethoa ho khethoa ha batsamaisi ba presynaptic ba sisteme ea mesolimbic dopamine ho hlahisa mokhoa o ts'episang bakeng sa kalafo ea botenya.

lumela hore baa fokola

Mosebetsi ona o tšehelitsoe ke DK065872 (ENP), F31 DA023760 (BMG, ENP), Moputso oa Smith Family Foundation Award of Excellence in Biomedical Research (ENP) le P30 NS047243 (Setsi sa Tufts bakeng sa Patlisiso ea Neuroscience).

khutsufalitsoeng

  • aCSF
  • mokelikeli oa 'mele o tsoang ka bongata
  • DAT
  • dopamine plasma membrane transporter
  • DIO
  • ho ja ho tlisoang ke botenya
  • DOPAC
  • dihydroxyphenylacetic acid
  • HPLC-EC
  • high performance liquid chromatography e nang le electrochemical detection
  • HVA
  • homovanillic acid
  • VMAT2
  • neuronal vesicular monoamine transporter
  • VTA
  • sebaka sa ventral tegmental

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