Likokoanyana tse jang lijo tse nang le mafura ha li bontše matšoao a mangata kapa matšoenyeho a amanang le ho tlosoa ha opiate-joalo: sepheo sa ho itšoara ka mokhoa o lemalang lijo (2011)

. Mongolo o ngotsoeng ka letsoho; e fumanehang ho PMC 2012 Oct 24.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

PMCID: PMC3480195

NIHMSID: NIHMS299784

inahaneloang

Liphuputso tsa pele li bontša hore ho itlopa joala ho tsoekere ho lebisa liphetohong tsa boitšoaro le tsa metsoako e tšoanang le tse bonoang ka ho lemalla lithethefatsi, ho kenyelletsa le matšoao a ho tlosoa ha opiate-joaloka ho khaotsa. Liphuputso li hlaha tse bontšang likarolo tse ngata tsa methapo ea maikutlo le boitšoaro ba ho lemalla ha liphoofolo li ja lijo tse nang le mafura a mafura. Sepheo sa thuto ea hona joale e ne e le ho sebelisa lijo tse matla le tse matla tse tsoekere le lihlahisoa tse mafura ho fumana hore na ho tlosoa ha opiate-joalo ho bonahala joang ka mor'a ho noa joala ho liphoofolo tsa linokoane tsa Sprague Dawley. Lihlopha tsa taolo li ile tsa fuoa ad libitum ho fumana lijo tse monate kapa mafura a tloaelehileng. Joale litsi tsohle li ile tsa fuoa liteko tsa betri ho lekanya matšoao a ho tlosoa ha opiate-joaloka, ho kenyelletsa matšoao a matšoao a mahlomola, ho tšoenyeha ho hoholo-le bo-maze-kelello, le ho ba le boikaketsi. Ha ho na lexxone-precipitated (3 mg / kg) kapa ho tlosoa ha motho ho hlekefetsoe ho hlokomolohuoa ka likhoto tse neng li bolokiloe lijong tse nang le mafura a monate o monate oa phepo e nepahetseng, lijo tse monate, tse mafura haholo tse tlatsitsoeng ka standard rodent chow, lijo tse nonneng. Ho feta moo, ho fokotseha ha 'mele ho 85%, e tsejoang hore e ka ba le liphello tse matlafatsang tsa tšebeliso e mpe ea tlhekefetso, ha ea ka ea ama matšoao a nang le lexone-precipitated of opiate-like withdrawal. Ka hona, ho fapana le liphuputso tse fetileng tse tlalehiloeng mabapi le likhoto tse nang le phepo ea li-sucrose, likhoto tse tloaelehileng li kopanya mefuta e monate ea mafura ha li bontše matšoao a ho tlosoa ha opiate-joaloka tlas'a maemo a lekiloeng. Ts'ehetso ea data ena khopolo ea hore ho sebelisoa ho feteletseng ha limatlafatsi tse fapaneng ho ka susumetsa boitšoaro bo amanang le ho lemalla ka litsela tse fapaneng, le hore boitšoaro bo ka khethollang "ho lemalla lijo" bo ka ba le karolo e thehiloeng mofuteng oa phepo ea lijo tse jeoang.

Keywords: ho itlopa joala, ho lemalla lijo, ho ja lijo tse ngata, ho tlohela lijo

Selelekela

Mekhoa ea li-Neural e khothalletsang le ho matlafatsa ho batla lijo le ho ja e boetse e theola boitšoaro bo amanang le tšebeliso e mpe ea lithethefatsi [-]. E thehiloe ho tsena tsa methapo ea pelo, ho 'nile ha boleloa hore ho ja lijo tse itseng ho ka boetse ha fella ka boitšoaro bo hlephileng ba ho lemalla [-]. Liphuputso tse fetileng tse tsoang ho laboratori ea rona le tse ling li fana ka maikutlo a hore ho fihlella habonolo ho tsoekere ho lebisa liphetohong tsa boitšoaro le liphetoho ho dopamine (DA) le mekhoa ea opioid e tšoanang, le hoja e nyane haholo, ho ba bonngoeng nakong ea lithethefatsi [].

Ka mekhoa e joalo ea ho lemalla lithethefatsi e amanang le ho noa joala ho tsoekere, bopaki ba ho khaotsa ho tlohela opiate ke thahasello e khethehileng. Re sebelisa mohlala oa liphatsa tsa laboratori oa ho itlopa joala ho ja tsoekere, re hlokometse hore ha ho e-na le mohanyetsi oa opioid oa nang le naxone, litoeba li bontša matšoao a mangata a ho tlohela, ho akarelletsa meno a thetsang, ho thothomela ha nako e telele, le ho sisinyeha ha hlooho, hammoho le matšoenyeho ho feta-maze . Ho feta moo, boitšoaro bona bo kopanngoa le ho fokotseha ha ho lokolloa ha DA nucleus accumbens le ho eketseha ha ho lokolloa ha acetylcholine [], ho se leka-lekane ha kelello e 'nileng ea bonoa nakong ea ho tlohela lithethefatsi tse' maloa tsa tlhekefetso [, ]. Matšoao a boitšoaro le a metsoako ea ho tlosoa ha opiate-joalo a boetse a hlokomeloa ntle le tšebeliso ea naloxone (ke hore, ka boithatelo) ka mor'a ho itima lijo ka likhoto tse nang le histori ea ho ja lijo tse tsoekere ka tsoekere []. Ba bang ba hlokometse hore likhoho tse nang le phihlelo ea ho fumana tsoekere e fokolang li fokotsehile mocheso oa 'mele ha tsoekere e tlosoa ka 24 h [] 'me e ka bontša matšoao a boitšoaro bo mabifi [], tse peli hape tse amoheletsoeng tsa ho tlohela. Ho feta moo, ho bontšitsoe hore lijo tse nang le tsoekere e phahameng li etsa hore ho be le matšoao a tšoenyehileng le hyperphagia, a bonahalang eka ke a tšebelisanoang ke mekhoa ea li-hormone e tsoang k'homphieutheng ea corticotrophin [].

Liphuputso tse ling li 'nile tsa hlahloba likarolo tsa ho lemala tse ka' nang tsa hlaha ha li arabela lijong tse ling tse thabisang, tse kang tse ngata tse mafura kapa tse mafura a monate. Naloxone e tlalehiloe ho hlahisa matšoao a ho tlohela opiate-joaloka likokoanyana ho fepa lijo tsa mokhoa oa ho ja lijo, tse nang le lijo tse fapa-fapaneng tsa mafura le tse tsoekere []. Haufinyane tjena, ho bontšitsoe hore litoeba tse pepesehileng lijong tse ruileng mafura li tla kopanela mekhoeng e mengata e fapaneng e bontšang ho lemala [, -], empa ho etsahala ha ho tlosoa ha opiate-joaloka ha ho e-s'o hlahlojoe ka mokhoa o hlophisitsoeng ho latela maemo a ho ja mafura haholo, eseng ho latela maemo a fokolang a fihletsoeng.

Kaha ebe mafura le tsoekere li ama tsamaiso ea opioid [], hore ka linako tse ling li-macronutrients tsena li jeoa ka ho feteletseng 'me li ka ba le karolo ea ho nona ho tlōla tse amanang le ho ja haholo [, ] mohlomong le ho lemalla lijo [, ], sepheo sa thuto ea hona joale e ne e le ho bona hore na ho tlosoa ha opiate-joaloka ho tlosoa ha likokoana-hloko ho bonoa ke likhoto tse bolokiloeng mananeong a ho finyella ho fokotsa lijo tse nang le tsoekere le mafura tse entseng hore ho jeoa ke lijo tse ngata. Ka litsela tse ngata, moqapi ona o tšoana le boemo ba motho ba ho ja, kaha likhahla tsa ho itlosa bolutu ho batho ba bang li atisa ho kenyelletsa motsoako oa li-macronutrients tsena [, , , ]. Ho feta moo, lipatlisiso tsa hona joale li hlahloba phello ea ho ja lijo tse ngata tse nang le tsoekere ka mahlahahlaha a mangata ha likokoanyana li le boemong bo tloaelehileng le ho fokotsa boima ba 'mele, kaha ho tsejoa hore boima ba' mele bo ka ba le liphello tsa lithethefatsi tsa ho hlekefetsa []. Ho feta moo, likhoto tse nang le boima bo boima ba 'mele li lokolla DA e eketsehileng ho feta ho laola boima ba' mele ha ho ja lijo tse tsoekere [], e ka 'nang ea fana ka maikutlo a ho ntlafatsa phello e thabisang ka boima ba' mele bo ka 'nang ba ama boima ba ho tlohela.

Lisebelisoa le mekhoa

Mekhoa e Akaretsang

Maqeba a banna ba Sprague-Dawley a ile a fumanoa Taconic Farms (Germantown, NY) mme a lula ka boeena ho Princeton University vivarium ka leseli la 12-h le fetohileng: 12-h mosi oa lefifi. Kamore e ne e lula ho 20 ° ± 1 ° C, mme liphoofolo li ne li e-na le ad libitum ho fihlella metsi ka linako tsohle le ho fihlella hola e tloaelehileng ea laboratori, LabDiet #5001 (PMI Nutrition International, Brentwood, MO; 3.02 kcal / g) joalokaha ho hlalositsoe ka tlaase. Mekhoa eohle e ile ea amoheloa ke Princeton University Institutional Animal Care le Komiti ea Ts'ebeliso. Lijo le litekanyetso li kenyelitsoe ka hare ho Lethathamo 1.

Lethathamo 1 

Kakaretso ea lihlopha le mekhoa ea teko ea liteko 1-4.

Exp. 1: Naloxone-precipitated le e ikemetseng opiate-like tlhahlobo ea ho itokolla ka likhoto fepa ka phepo e nepahetseng, fat-le-tsoekere e ruileng

Li-rats (315-325 g) li arotsoe ka lihlopha tse 'nè tse nang le boima ba motsoako (n = 10 / sehlopha)' me li abeloa ho tse ling tsa maemo a latelang a phepo bakeng sa matsatsi a 25: (a) 2-h letsatsi le leng le le leng ho fihlella mafura a monate o monate (Patlisiso Lijo tse ncha, New Brunswick, NJ, #12451; 45% mafura, 20% protheine, 35% ea lik'habohaedreite, 4.7 kcal / g) ho qala 6 h ka mor'a ho qala ha lefifi, ka standard rodent chow e fumanehang feela 22 h letsatsi; (b) 2-h ho fihlella ho phofo e monate ka Mantaha, Laboraro le Labohlano (MWF) le ad libitum ho fihla ho standard rodent chow nakong e setseng; (c) ad libitum monko o monate o monate; le (d) ad libitum sekhetho se tloaelehileng (LabDiet #5001, International PMI ea Phepo e nepahetseng, Richmond, IN; 10% mafura, 20% protheine, 70% lik'habohaedreite, 3.02 kcal / g). Lijo li ne li nkeloa sebaka habeli ka beke. Lijo tsa lijo li ne li lekanyetsoa letsatsi le leng le le leng (pele le ka mor'a nako ea ho fumana 2-h, kapa nako e lekanang bakeng sa ad libitumlihlopha tse feletseng). Boima ba 'mele bo ne bo boetse bo lekantsoe nakong ena ka matsatsi a 1-7 le matsatsi a 18-24 ea ho fihlella.

1a. Ho hlahlojoa ha Naloxone ka potlako

Ka matsatsi a 26 le likhoka tsa 27 li ne li abeloa ho hlahlojoa hore li tlosoe. Liteko tsena li ne li jaletsoe ka matsatsi a 2 ho etsa bonnete ba hore liteko li ne li khannoa haufi le tšimoloho ea nako ea tloaelo ea 2-h ha ho khoneha bakeng sa rat e 'ngoe le e' ngoe. E le ho hlahloba lipontšo tsa somatic ea ho tlosoa ha opiate-joaloka, likokoanyana li ne li tsamaisoa le mohanyetsi oa opioid naloxone (Sigma, St. Louis; 3 mg / kg, sc). Likokoanyana li ne li tsamaisoa ka 6 h kamora ho qala ho potoloho ea lefifi, ha ho fihlella lijo tse monate ho ne ho tloaelehile ho qala. Li-ratsane tsa 2-h MWF li ne li e-na le nako ea 46-h ea ho tlosoa ha likheo tse ntle pakeng tsa nako ea tsona ea ho ba teng nakong ea beke (le hoja ba ne ba e-na le likhahla tse tloaelehileng tse fumanehang nakong ena), hape ba lahleheloa ke lijo tse monate ka mafelo-beke. Ka hona, ho tiisa nako ea ho hlekefetsoa ha 46-h, re netefalitse hore likhohlo tsohle li hlahlojoa ha li na le 46 h ea ho tlosoa ha mafura a monate. Metsotso e leshome ka mor'a hore e entsoe, likotlolo li ne li kenngoa kahare ea polasetiki e nang le Bed-o-Cobs (The Anderson Co., Maumee, OH), le matšoao a ho tlosoa ha 'ona ho tlalehoa 5 min ka motho ea shebeletseng maemo a sa lebelloang. Mekhoa ea ho loma ka marang-rang, ho koala ho sireletsa ho itšireletsa, ho phunya ntja ea metsi, meno e thetsang, ho sisinyeha ha hlooho, ho thothomela ka pele ho moo, ho phalla ha cage le ho itlhophisa ho ile ha tlalehoa bakeng sa rat e 'ngoe le e' ngoe, 'me liketsahalo tsohle tsa boitšoaro bona li ile tsa akaretsoa ho hlahisa sekoto , ho sebelisa mokhoa o fetotsoeng ho tsoa litlalehong tse ling [, ].

1b. Ho etsa tlhahlobo ea ho itokolla ka tšohanyetso

Ho fumana hore na ho itšepa ho ka bonoa joang ka ho tlosa lijo tse monate feela (ie, ntle le naloxone), likhofu li ile tsa fuoa monyetla oa ho fihlella feela standard rodent chow bakeng sa libeke tsa 3. Ebe, likhofu li khutliselitsoe mananeong a bona a nakong ea lijo bakeng sa matsatsi a 14. Nakong ea nako e latelang ea mafura a monate a monate, liphoofolo tsohle li ne li bolokiloe ka mokhoa o tloaelehileng oa ho tsuba ha 46 h. Qetellong ea 46 h, ha sehlopha sa liteko se ne se atisa ho fumana ho fumana mafura a monate o monate, ho e-na le hoo li ne li hlahlojoa bakeng sa matšoao a ho tlosoa ha motho.

Exp. 2: Ho hlahlojoa ha li-naloxone le ho thibela ho itokisetsa ho itšireletsa mafung ho fepa standard rodent chow ka lijo tse sa phetseng hantle tse nang le tsoekere le mafura

Tlhahlobo ena e ile ea sebelisa tlhahlobo e eketsehileng ea ho tlosoa ha opiate-joaloka ho tlosoa ha opiate, mohope o phahameng le ho feta, ho etsa qeto ea likarabo tse peli tse tšoenyang le tse tšoenyang tse kang ho tlohela lijo tse monate. Li-rats (350-400 g) li arotsoe ka lihlopha tse tharo tse nang le litekanyo (n = 8 / sehlopha) 'me li bolokiloe ka ad libitum ho tsuba le metsi a tlatsitsoeng ka matsatsi a 28: (a) 12-h ho fumana motsoako o phahameng oa tsoekere, o mafura haholo (4.48 kcal / g; 35.7% mafura, 64.3% sucrose; botoro, tsoekere e phofshoana, e lokiselitsoeng ho rona laboratory); (b) ad libitum ho fumana tsoekere e tšoanang le mafura a motsoako (c) ad libitum chow. Lijo li ile tsa nkeloa sebaka ka makhetlo a mabeli beke le beke, ka nako eo liphoofolo li neng li lekoa.

2a. Ho etsa tlhahlobo ea ho itokolla ka tšohanyetso

Ka letsatsi la 28, likotlolo tsohle li ne li behoa ka mokhoa oa ho ja ad libitum standard rodent chow. 24 h le 36 h hamorao litsu tsohle li ile tsa hlahlojoa ka matšoao a somatic ea ho tlosoa ha opiate-like e le ho fumana hore na palo e akaretsang ea ho tlohela, e hlalositsoe ho Exp. 1a. Ebe, ho leka ho tšoenyeha, ka nako eo liphoofolo li ne li behoa ka 5 min ka bo-maze-bohareng bo holimo []. Mochine o ne o e-na le matsoho a mane, ka bophara ba cm 10 cm ka bolelele ba cm 50, mme o ne o phahame ka cm 60 ka holimo. Matsoho a mabeli a fapaneng a ne a koaletsoe ka marako a phahameng a opaque, ha matsoho a mang a mabeli a se na marako a sireletsang. Tlhahlobo e ne e khannoa tlas'a leseli le lefubelu ho fokotsa pherekano ho likhoto tsa circadian cycle. Likokoanyana li ne li behiloe bohareng ba maze ka sehlooho sa hlooho se fetisetsoa letsohong le bulehileng kapa le koetsoeng. Tlhahlobo e 'ngoe le e' ngoe ea bo-maze e ne e ngotsoe ka video 'me hamorao e fumanoa ka nako e sebelisitsoeng ka hlooho, mahetleng le lipale tsa pele ka letsoho le bulehileng, letsoho le koaletsoeng kapa bohareng ba maze ka motho ea shebileng a sa bone boemo ba ho ja.

2b. Tlhahlobo ea ho itokolla ka Naloxone-precipitated

Ho latela liteko ho Exp. 2a, liphoofolo tsohle li khutliselitsoe lijong tsa tsona bakeng sa matsatsi a 21 ebe li tsamaisoa le naloxone (Sigma, St. Louis; 3 mg / kg, sc). Metsotso e leshome ka mor'a ente, likarolo li ne li hlokomeloa ka matšoao a mangata a ho tlohela le ho tšoenyeha ho hoholo-le-maze (joalokaha ho hlalosoa ho Exp. 2a).

Exp. 3: Naloxone-precipitated opiate-like tlhahlobo ea ho itokolla ho likhoto tse bolokiloeng ka mokhoa o tloaelehileng oa rodent chow le ka lijo tse nang le metsi tse nang le tsoekere le mafura

Lijo tse nkiloeng ho Exp. 1 le 2 li ne li tiile; ka mor'a moo re ile ra leka ho ja lijo tsa metsi e le hore re laole liphello tsa tlhaho, kaha matšoao a ho tlosoa ha opiate-joaloka phoofolo ea rona ea ho ja lijo tse tsoekere ea tsoekere e ne e akarelletsa tšebeliso ea tharollo ea sucrose [, ], 'me ho na le phapang e tsebahalang liphellong tseo lijo tse tiileng le tsa metsi li ka ba le boitšoaro bo kotsi [, ]. Li-rats (300-375 g) li arotsoe ka lihlopha tse 'nè tse nang le litekanyo (n = 8 / sehlopha)' me li bolokiloe matsatsi a 28 ka ad libitum chow e tlatsitsoe ka: (a) 12-h ho fumana emulsion ea oli, tsoekere le metsi (3.4 Kcal / mL, 35% mafura, 10% tsoekere; Mazola® Mafura a Majoe, sucrose, metsi a pompo le 0.6% Emplex, Li-Caravan Lijo , Lenexa, KS, e lokiselitsoeng ka laboratori ea rona), le chow; (b) 12-h ho fumana ho netefatsa ha vanilla (1.06 Kcal / mL, 30% mafura, le 30% tsoekere, Abbott Laboratories, Abbott Park, IL) le chow; (c) 12-h ho fumana tharollo ea 10% (w / v) ea sucrose (0.4 Kcal / mL) le chow, kapa (d) ad libitum chow. Ho lokisa emulsion, metsi a ne a futhumetse ho 75-80 ° C mme a kenyelletsoa litsong tse ling. Emulsion e ne e tsoakane ka lebelo le leholo bakeng sa minara ea 5 ebe e qhibiliha ka ho hlapa ho hlatsoa ho fihlela e fihla 20 ° C. Lijo tsohle (haese ka chow e tloaelehileng) li ne li le metsi 'me li ne li hlahisoa thupong ea ho noa e fumanoang mangolo. Lijo li ne li nkeloa sebaka letsatsi ka leng 'me liphoofolo li ne li bekoa beke le beke.

Tlhahlobo ea ho itokolla ka Naloxone-precipitated

Ka mor'a matsatsi a 28 lijong tse abetsoeng, likhofu li ne li tsamaisoa ka naroxone (3 mg / kg, sc). Metsotso e leshome ka mor'a hore e entsoe, likhofu li ne li behoa holim'a bo-maze-bohale bo phahameng haholo joalokaha ho hlalosoa ka Exp. 2a. Hang-hang ka mor'a tlhahlobo ea bo-maze e phahameng ea bo-5, litsuoa li ne li behoa kamoreng ea liketsahalo tse bulehileng ka tlas'a leseli le khubelu (MED Associates, Georgia, VT, 30.5 cm e mahlakoreng a mahlakoreng a li-acrylic le li-photocells tse nang le mahlaseli a 16 ho tse ling tse tharo. ). Sebaka seo kaofela se ne se le 43.2 cm × 43.2 cm. Nako e 'ngoe le e' ngoe e ile ea kenngoa bohareng ba tšimo 'me ea fuoa nako ea ho lumellana ha metsotso ea 10 pele tlhahlobo e qala [, ]. Ka nako eo, mosebetsi oa ho lokisa, o hlalosoang e le ho phunyeha ha sefate sa infrared, o ile oa hlahlojoa bakeng sa 20 min.

Exp. 4: Naloxone-precipitated opiate-like tlhahlobo ea ho itokolla ho likhoto ka boima ba 'mele bo fokotsehileng

E le ho hlahloba hore na lipontšo tsa ho khaotsa li ka fetisoa boima bo fokolang ba 'mele, likarolo tse nang le boima ba' mele (283-345 g) li bolokiloe ka matsatsi a 21: (a) 2-h letsatsi le leng le le leng ho fihlella mafura a monate o monate (Lijo tsa Lipatlisiso, New Brunswick, NJ, #12451, e sebelisitsoeng ho Exp. 1) ho qala 6 h ho qala ho potoloho ea lefifi, ka tloaelo rodent chow e fumanehang feela bakeng sa 22 h ka letsatsi (n = 10), kapa (b) ad libitum sekoti se tloaelehileng se nang le 2 h ea ho fumana phow e nkhang hamonate feela matsatsi a mabeli (letsatsi la 2 le letsatsi 22 kapa 23; sehlopha se monate sa Fat-Fat, n = 9). Ho nkoa lijo ka letsatsi le letsatsi ho 6 h le 8 h kamora ho qala ho potoloho ea lefifi; lijo li ne li nkeloa sebaka habeli beke le beke.

4a. Ho tloaeleha ho hlahloba boima ba 'mele

Ka letsatsi 22, 6 h nakong ea lefifi, likhofu kaofela li ne li tsamaisoa le naloxone (3 mg / kg, sc). Metsotso e leshome ka mor'a hore e entsoe, likhofu li ne li hlokomeloa ka matšoao a ho tsuba le ho phahama ho hoholo-joalo ho hlalositsoe ho Exp. 2a.

4b. Ho fokotsa tlhahlobo ea 'mele ea ho itokolla boima ba' mele

Lipotlolo tsa 2-h tsa letsatsi le letsatsi tse monate li ne li fokotsoa ho ba 85% boima ba 'mele ka nako ea 7 ka ho fokotsa ho fumanoa ha letsatsi le letsatsi le le leng ho ea mokokotlo (3 g) kapa pelong e le' ngoe (5 g) ho halofo ea pente (2 g) kapa pellet e le 'ngoe (3.5 g). Palo ea lijo e fanoeng e ile ea fetoloa bakeng sa rat ka 'ngoe ho ea ka tekanyo ea tahlehelo ea boima ba' mele. Sehlopha se setle se monate sa Fat se boetse se fokotsoe ho ba 85% boima ba 'mele ka nako ea 7 ka ho fokotseha ha maemo a tloaelehileng a letsatsi le leng le le leng a fumaneha ho pelletsane ea 1-2. Lihlopha sehlopheng sena li ile tsa fuoa 2-h ho fumana phofu e monate e monate ka lekhetlo la boraro ka letsatsi 30 kapa 31. Liteko tsa ho khaotsa (lipontšo tsa somatic le maze-maze) li ile tsa etsoa hape ka letsatsi la 29 joalokaha ho hlalositsoe ho Exp. 1a le 2a.

4c. Ho tloaelehile hore boima ba 'mele bo sebetse

Ka mor'a ho hlahlojoa ka boima ba 'mele bo fokolisitsoeng, litsie kaofela li ile tsa fuoa ad libitum ho fihlella boemong bo tloaelehileng ba khoeli e le 'ngoe ho ba lumella ho khutlela boima ba' mele bo tloaelehileng ba lilemo tsa bona. Joale, liphoofolo tsohle li khutliselitsoe lijong tsa bona tsa liteko bakeng sa matsatsi a 14. Lihlopha tsa sehlopha se nang le mahlaseli a mafura a Fat Sweet-Fat li ile tsa fuoa monyetla oa ho fumana oli e monate hape ka letsatsi la leshome le metso e mene la ho fihlella lijong tsa tlhahlobo ea ho hlahloba e le ho bona hore na boitšoaro bo bakoa ke ho itlopa lijo kapa ho ja lijo feela. Joale, 6 h kamora ho qala ha potoloho e lefifi, naloxone (3 mg / kg, sc) e ne e laoloa. Metsotso e leshome ka mor'a hore e entsoe, likhofu li ne li behoa ka kamoreng ea liketsahalo tsa k'homphieutha e sa bulehileng tlas'a leseli le khubelu, joalokaha ho hlalositsoe ho Exp. 3a. Nako e 'ngoe le e' ngoe e ne e behoa bohareng ba kamore ea ho lokisa, 'me lintlha tsa liketsahalo li lekantsoe bakeng sa minara ea 10.

4d. Ho fokotseha ha tlhahlobo ea boikoetliso ba boima ba 'mele bo fokotsehileng

Ho latela Exp. 4c, boima ba 'mele ba likhoto bo boetse bo fokotsoe ho 85% joalokaha bo hlalositsoe ka holimo nakong ea matsatsi a 7. Ho hlahlojoa ha mesebetsi ea boipheliso ho ile ha tšoaroa ka tsela e hlalositsoeng ho Exp. 3c.

Tlhahlobo ea Litekanyetso

Lintlha li ile tsa hlahlojoa ka tsela e le 'ngoe le litlhahlobo tse peli (ANOVA) tse nang le Newman Keuls kapa lithuto tsa Tukey ha ho hlokahala, kapa tlhahlobo ea T ea Seithuti. Bakeng sa boitsebiso bo phahameng ba Maze, mosebetsi oa matsoho o bulehileng o ne o nkoa e le nako ea kakaretso eo rat e 'ngoe le e' ngoe e e sebelisang matsohong a maze []. Lintlha tsa boitsebiso bo fumanehang pele li ne li hlahlojoa ka tsela e le 'ngoe bakeng sa tekanyo e' ngoe le e 'ngoe ea ho tsoa ha metsi' me ka tsela e 'meli ANOVA e bapisa litekanyo tsa ka hare ho sehlopha le ho fokotsa boima ba' mele, hammoho le mehato e pakeng tsa sehlopha. Phoso e hlahisitsoeng ka letsoho lena ke phoso e tloaelehileng ea se boleloang.

Results

Exp. 1: Matšoao a khatello ea kelello ea Naloxone kapa a se nang matšoao a sa tšoaneng ha aa ka a hlokomeloa ka likhoto tse fuoeng mafura a monate a phetseng hantle

Dintlha tsa boima ba 'mele le boima ba' mele

Lintlha tsa ho kenya lipotlolo tsena li tlalehile pele []. Ho akaretsa ka bokhutšoanyane liphuputso tseo, ha li bapisoa le lihlopha tsa taolo, likhoto tse nang le 2-h letsatsi le leng le le leng le ho fumana 2-h MWF ho lijo tse nang le monate o monate o nang le phepo e nkiloeng ka bongata haholo ka chow e ntle ka 2 h ea ho fihlella. Boima ba 'mele ba liphoofolo tsena bo eketsehile ka lebaka la lijo tse kholo' me joale li fokotseha pakeng tsa menoana ka lebaka la ho itšireletsa ka boomo ho latela likhao tse latelang. Leha ho le joalo, ho sa tsotellehe phetoho ena ea boima ba 'mele sehlopha se nang le phihlelo ea mafura a monate letsatsi le leng le le leng se fumane boima bo boholo ho feta sehlopha sa taolo se nang le chow e tloaelehileng e fumanehang ad libitum. Ho feta moo, ha ho hlahlojoa phaello ea boima ka nako ea thuto, ho bile le phapang pakeng tsa lihlopha (F(3,39) = 7.74, p <0.001), le liphoofolo tseo tse nang le phihlello ea letsatsi le letsatsi ea 2-h ho chow e nang le mafura a mangata e fumana boima bo fetang ba taolo e tloaelehileng ea li-chow (108.6 ± 6.2 g vs. 75.4 ± 3.8 g, ka ho latellana; p<0.001) le litsamaiso tse fepehileng ka lijo tse nang le mafura a monate (88.3 ± 4.9 g; p<0.05). Ntle le moo, likhoto tse nang le phihlello ea 2-h MWF lijong tse nang le mafura a monate li bile le boima bo fetang ba li-chow-fed (95.0 ± 4.6 g vs. 75.4 ± 3.8 g, ka ho latellana; p

Ho tlohela liteko

Ha a fuoa naloxone, ho ne ho se na phapang pakeng tsa ho tlohela likarolo bakeng sa boitšoaro ba somatic bo bontšitsoeng pakeng tsa lihlopha (F(3, 36) = 2.71, p = ns). Mekhoa ena e ne e kenyeletsa ho thothomela ha pele ho nako, ho pholletsa le cage, ho loma le ho sireletsa (p = ns bakeng sa mong le e mong; bona Feie. 1). Ntja e metsi e sisinyehileng e ne e sa hlokomeloe ho sehlopha leha e le sefe.

Setšoantšo sa 1 

Exp. 1: Mehlala ea matšoao a somatic ea ho tlosoa ha naloxone-ho se hoholo (ho bolela ± SEM). Ho ne ho se na phapang ea statistically har'a lihlopha ka boitšoaro bo lekantsoeng. Lipontšo tsa Somatic ka mehlala e sa tšoaneng (Ntja e omileng e sisinyeha, hlooho e sisinyeha, ...

Mehlala ea matšoao a ho khaotsa ho tlohela ka morao ho tlohela ho khaola mafura a monate a hlalositsoe Feie. 2. Ho ne ho se na bohlokoa har'a lihlopha pakeng tsa palo eohle ea likhahla tsa ho tlohela (F(3, 36) = 2.04, p = ns). Litšoantšiso tse bontšang bohlale li bontša hore ha ho na phapang pakeng tsa lihlopha bakeng sa ho thothomela ha pele ho nako, ho palama ho paw kapa ho koala ho sireletsa (p = ns bakeng sa bohle). Bohlokoa bo ne bo bonoa har'a lihlopha maemong a ho tšela kagelo (F(3, 36) = 4.66, p <0.05). Post hoc Liteko tsa Tukey li senoletse hore likhohlopo tsa 2-h tsa letsatsi le leng le le leng li ne li bontša hore li fokotseha haholo ho feta ha ad libitum Liw rats (p <0.01) kapa ad libitum Rats e monate-Fat (p <0.05). Hape, lintja tse metsi li ne li sa sisinyehe sehlopheng sefe kapa sefe.

Setšoantšo sa 2 

Exp. 1: Lipontšo tsa Somatic tsa ho itšehla thajana (ho bolela ± SEM). 2-h Maqeba a mafura a letsatsi le leng le le leng a monate a ne a bontša ho se hokae maemo a ho fapana ha cage ho feta Ad libitum Li-rats kapa Ad libitum Lipoe tse monate, *p <0.05. Matšoao a ho ikhula ...

Exp. 2: Matšoao a mangata a hlahang, a tšoaetsoang ka ho toba, kapa a matšoao a matšoenyeho a bohale bo phahameng a sa kang a hlokomeloa ka likhoto a ne a fepa mafura a monate ho ea ka sekhahla sa 'ona

Dintlha tsa boima ba 'mele le boima ba' mele

Liphoofolo tse neng li le har'a sehlopha sa 12-h se monate sa Fat + Chow se ne se ja lijo tse ngata tse monate nakong ea pele ea phihlelo ea letsatsi le leng le le leng ha li bapisoa le liphoofolo tse ts'oanang le tsona ad libitum Lijo tse monate-tsa Fat + Chow (F(2, 21) = 13.16, p <0.001, letsatsi la 28 la phihlello ea lijo, 5.6 vs. 1.1 g, ka ho latellana). Ka letsatsi la 28 la phihlello ea lijo, sehlopha sa 12-h Sweet-Fat se ile sa ja 3.5 ± 0.9 g ea chow, the ad libitum Sehlopha se monate sa Fat se ne se ja 0.68 ± 0.7 g ea chow, le ad libitum Sehlopha sa Chow se ne se ja 2.3 ± 1.5 g ea chow ka hora ea pele. Ho sa tsotellehe phapang pakeng tsa tlatsetso ea mafura le monate, letsatsing la 28 ho ne ho se na phapang e nang le phapang pakeng tsa lihlopha ka kakaretso ea lik'hilojule tse jang nako ea 24-h (F(2, 22) = 0.62; p = ns; 12-h Nako e monate: 82.8 ± 2.6 Kcal, ad libitum E monate-Fat: 77.3 ± 7.8 Kcal, ad libitum Chow: 83.2 ± 6.8 Kcal). Ka letsatsi la 28, boima ba 'mele ea likhoto bo ne bo sa fapane ka ho fapaneng har'a lihlopha (F(2, 23) = 1.87, p = ns). Ho feta moo, ho hlahloba boima bo fumanoeng ho feta nako ea thuto ha hoa ka ha e-ba le phapang e khōlō har'a lihlopha (F(2, 21) = 1.31, p = ns).

Ho tlohela liteko

Ho ne ho se na phapang e ikarabellang ea ho tlohela likarolo tsa likarolo tse boletsoeng har'a lihlopha tsa 24 h (F(2, 23) = 0.24, p = ns; 12-h Monate-Fat sehlopha = 11.5 ± 2.6, ad libitum E monate-Fat sehlopha = 13.6 ± 2.6; ad libitum Sehlopha sa sehlopha = 13.4 ± 1.8) le 36 h (F(2, 23) = 0.17, p = ns; 12-h Monate-Fat sehlopha = 11.8 ± 2.6, ad libitum E monate-Fat sehlopha = 12.1 ± 1.4; ad libitum Chow sehlopha = 10.5 ± 2.0) ka mor'a hore liphoofolo li amoheloe ke lijo tse monate. Palo ea lenane e kenyelletsa mekhoa ea ho itlhoekisa, ntja e metsi e sisinyeha, ho phalla ha cage, ho thothomela ha pele ho nako, ho loma le ho sireletsa ho sireletsa (bakeng sa papiso e 'ngoe le e' ngoe e bohlale, p = ns). Ha ho na maemo a ho sisinyeha a ileng a bonoa ho 24 h le 36 h nako ea nako.

Mabapi le mohoelelo o phahameng haholoanyane, kamora 24 h ea ho hlekeheloa ho ne ho e-na le phapang e nang le phapang pakeng tsa lihlopha ho latela nako e sebelisoang ka letsoho le bulehileng (F(2, 23) = 3.77, p<0.05; 3.1 ± 1.4 s, 20.0 ± 6.0 s le 15.4 ± 4.7 s, ad libitum E monate-Fat, 12-h e monate-'me le ad libitum Chow ka ho latellana), le likhoto tse neng li bolokiloe ad libitum Lijo tse monate li qeta nako e fokolang letsohong le bulehileng ho feta 12-h sehlopha se monate sa Fat kapa ad libitum Sehlopha sa Chow (p <0.05). Ho 36 h ea bohloki, ha ho na litlamorao tse bonoeng ka nako e sebelisitsoeng letsohong le bulehileng la maze e kholo (F(2, 23) = 0.22, p= ns; 26.3 ± 7.6 s, 30.0 ± 10.0 le 23.4 ± 7.2, ad libitum E monate-Fat, 12-h e monate-'me le ad libitum Khetha ka ho latellana).

Ho latela lengxone, ho ne ho se na phapang e nang le lintlha tse ngata ka ho tlohela likarolo tse ngata tsa boitšoaro ba somatic tse bontšitsoeng har'a lihlopha (F(2, 23) = 0.64, p = ns). Palo ea lintlha tsa ho tlohela e ne e le 8.4 ± 2.5 bakeng sa sehlopha sa X -UMX-h se monate, 12 ± 11.5 bakeng sa ad libitum Sehlopha se monate-Fat le 11.4 ± 1.7 bakeng sa ad libitum Sehlopha sa Chow. Palo ea lenane e kenyeletsa boitšoaro ba meno a ho pheta-pheta, ho itlhoekisa, ho phalla ha cage, ho thothomela ha pele ho moo, ho loma ha paw le ho koala ho sireletsa (bakeng sa papiso e 'ngoe le e' ngoe e bohlale, p = ns). Ha ho na maemo a ho sisinyeha kapa ntja e tsitsitseng e sisinyehang.

Exp. 3: Matšoao a Naloxone-precipitated somatic kapa matšoao a matšoenyeho ka tsela e phahameng ea ho feta e ne e sa hlokomeloe ka likhoto a fepa metsi a phahameng a mafura, a phahameng-sucrose lijo

Boitsebiso ba tlhahiso

Ka beke ea boraro ea ho fumana lijo, ho ne ho e-na le phapang pakeng tsa lihlopha tsa tsona tsa ho qeta lihora tsa pele (emulsion ea tsoekere = 32% ea kcal, Vanilla Ensure = 27% ea kcal, le 10% Sucrose = 24% ea kcal ea ho kenyeletsa letsatsi ka leng; F(2, 27) = 39.40, p <0.001). Ho ne ho boetse ho na le phapang e kholo lipalo pakeng tsa lihlopha mabapi le ts'ebeliso ea bona ea letsatsi le letsatsi ea rodent chow (F(3, 78) = 22.86, p <0.0001), le liphoofolo tse nang le lijo tse hlabosehang tse fumanehang li bontša ho fokotseha ha lijo tsa tsona tsa litoeba tse tloaelehileng ka letsatsi la 28 (23 ± 3 Kcal: Emulsion ea oli ea tsoekere; 30 ± 4 Kcal: Netefatsa ea Vanilla; 71 ± 2 Kcal: 10% Sucrose ) mabapi le ad libitum Sehlopha sa Chow (101 ± 4 Kcal). Le hoja ho ne ho e-na le phapang e bonoang har'a lihlopha ka kakaretso ea khalori ea letsatsi le letsatsi (F(3, 27) = 3.50, p <0.05), papiso e mengata e latellanang e bontšitse hore ho ne ho se na liphapang tse boletsoeng ha sehlopha ka seng se ne se ikemetse ha se bapisoa le sehlopha sa taolo se jang chow (101 ± 4 Kcal), p = ns maemong 'ohle (118 ± 13 Kcal: emulsion ea oli ea tsoekere; 93 ± 11 Kcal: Li-vanilla Li tiise; 85 ± 6 Kcal: 10% Sucrose). Ho feta moo, lenane la li-sucrose tse hlileng li jang (ka ligrama) li ne li tsitsana lihlopheng le sehlopha se seng le se seng se jang 3-4.5 g ea tsoekere / letsatsi le leng le le leng, esita le ho fana ka lijo tse fapa-fapaneng (F(2, 20) = 2.32, p = ns). Qetellong ea libeke tsa 4, ho ne ho se na ho se tšoane ha boima ba 'mele har'a lihlopha (F(3,31) = 0.25, p = ns). Leha ho le joalo, ha ho hlahlojoa phaello ea boima ka nako ea thuto, ho ne ho e-na le phapang pakeng tsa lihlopha (F(3,31) = 3.67, p <0.05), le liphoofolo tseo tse jang emulsion ea oli ea tsoekere li fumana boima bo fetang ba taolo e fepetsoeng ke Chow (123 ± 23 g vs. 67 ± 6 g, ka ho latellana, p <0.05).

Ho tlosoa ha data

Ha o behoa holim'a bo-maze-bohareng bo phahameng le ho feta ka li-injection tsa naloxone, liphoofolo tse nang le 12-h 10% Kakaretso ea katleho e qeta nako e fokolang letsohong le bulehileng la bo-plus-maze li bapisoa le litaelo tse fepehileng (t(9) = 2.58, p <0.05; 52 ± 7 vs. 75 ± 3 s). Ha ho liphapang tse ling tse ileng tsa tsejoa hara lihlopha (12-h Sugar-oil emulsion group = 54 ± 11 s letsohong le bulehileng; 12-h Vanilla Netefatsa sehlopha = 75 ± 3 s letsohong le bulehileng). Tlhatlhobo ea data e bulehileng ea maze e senotse hore sehlopha sa 12-h 10% Sucrose se ekelitse ts'ebetso ea basebetsi (F(3, 29) = 3.65, p <0.05) ha e bapisoa le ad libitum Sehlopha sa Chow (743 ± 70 le 512 ± 57 sepheo sa boipheliso, ka ho latellana). Ha ho na phapang e meng e ileng ea tsejoa har'a lihlopha tsa bohareng ba tšimo (12-h emulsion ea oli ea Sugar = 561 ± 71 dipalo tsa boipheliso; 12-h Vanilla Etsa bonnete ba sehlopha = 576 ± 58 liphuputso tsa boipiletso).

Exp. 4: Matšoao a Naloxone-precipitated somatic kapa matšoao a matšoenyeho boemong bo phahameng bo boholo ba linakong tse nang le mafura a binge-mafura ha aa ka a bonoa ha a fokotsoe ho 85% boima ba 'mele

Dintlha tsa boima ba 'mele le boima ba' mele

Ho qala ka beke ea bobeli ea ho fumana mafura a monate, likhofu tsa sehlopha sa 2-h Daily Sweet-Fat li ne li ja lik'hilojule tse ngata ka 2 h ea ho fumana lijo tse monate tse nang le monate (66.8% ea kakaretso ea letsatsi le leng le le leng), e tsitsitseng le tlaleho ea rona ea pele e sebelisa mohlala ona [] 'me e fana ka maikutlo a boitšoaro bo itekanetseng ba ho ja. Sehlopha se setle se monate sa Fat se ne se ja 24.6 ± 12.5 kcal ka letsatsi 2 le 48.1 ± 14.1 kcal letsatsing la 22 kapa 23 ho tloha lipaleng tse monate tse monate. Ha boima ba 'mele bo tloaelehileng, mefuta e mengata ea ANOVA (e nang le khalemelo ea Greenhouse-Geisser) e bontšitse sehlopha sa bohlokoa × ho sebelisana ha nako (F(1.63, 27.70) = 21.28, p <0.001). Liteko tsa Post-hoc li senotse boima ba 'mele bo boima haholo bakeng sa sehlopha sa 2-h Daily Sweet-Fat ha se bapisoa le sehlopha sa Acute Sweet-fat (letsatsi la 8: t(1, 17) = 2.28, p <0.05, letsatsi la 12: t(1, 17) = 2.63, p <0.05, le letsatsi la 16: t(1, 17) = 2.94, p <0.01). Ho feta moo, ha ho ne ho hlahlojoa boima ba 'mele matsatsing a pele a 16, likhoto sehlopheng sa 2-h Daily Sweet-fat li fumanoe li se li le boima ho feta sehlopha sa Acute Sweet-fat (81.0 ± 4.1 g vs. 45.3 ± 4.5 g, ka ho latellana; F(1, 18) = 33.83, le <0.001). Ha liphoofolo li fokotsoa ka boima ba 'mele, mehlala e kopaneng t-botho ba bontšitse hore 'mele oa boima ba lihlopha tseo ka bobeli o fokotsehile haholo (t(9) = 25.50, p <0.001 le t(8) = 19.93, p <0.001, 2-h Sweet-Fat Chow le Acute Sweet-fat Chow, ka ho latellana).

Ho tlosoa ha data

Boima bo tloaelehileng, phapang e le 'ngoe feela e pakeng tsa lihlopha e senola hore likhopo tsa fatše tsa 2-h tsa mafura li ne li bontša liketsahalo tse fokolang tsa ho tšela kage ho bapisoa le lipotlolo tse nkhang hamonate tse ntle (2.3 ± 0.4 vs. 4.5 ± 0.9; F(1, 16) = 5.54, p <0.05; Feie. 3). Leha ho le joalo, ha ho na ho se tšoane ho ileng ha bonoa ka index eohle ea ho tlohela (2-h Daily Sweet-mafura: 9.4 ± 1.2; Mafura a monate a monate: 12.5 ± 2.0; F(1, 16) = 2.00, p = ns). Sena se ne se kenyelletsa mekhoa ea ho itšoara, ho sisinya hlooho, ho itlhopha le ho hōlisa (p = ns bakeng sa mong le e mong). Ha ho likhoto tse bontšang menyetla leha e le efe ea meno ea ho qoqa.

Setšoantšo sa 3 

Exp. 4: Ho fapana ka cage (bolela ± SEM). Ha boima bo tloaelehileng, likhoka tsa fatše tsa 2-h tsa mafura li bonts'a liketsahalo tse fokolang tsa ho fapana ha cage ho bapisoa le Ad libitum Tsela ea ho laola, *p <0.05.

Ha boima ba 'mele bo fokotsehile, ho ne ho se na phapang e nang le likhetho pakeng tsa lihlopha ka linako tse ling tsa matšoao a ho tlohela, joalokaha ho bonngoe ke lintlha tsa index (F(1, 16) = 0.49, p = ns). Palo ea index ea ho tlosoa ke 13.0 ± 3.2 sehlopheng se mafura a mafura a monate ho latela 10.8 ± 1.2 sehlopheng sa fatše sa mafura a letsatsi le letsatsi sa 2-h. Palo ea lenane e kenyeletsa boitšoaro ba meno a ho pheta-pheta, ho hōlisa, ho itlhoekisa, ho phalla ha cage, ho thothomela ha pele ho moo, ho tsuba le ho laola boitšoaro. Ha ho na maemo a ho sisinyeha a ileng a hlokomeloa.

Ka tekanyo e phahameng ea ho feta-maze, nako e sebelisitsoeng letsohong le bulehileng ha ea ka ea fapana le sehlopha pele ho fokotseha ha boima (2-h) sehlopha sa mafura a letsatsi le letsatsi: 22.4 ± 7.7; Sehlopha se monate-Fat Chow sehlopha: 17.4 ± 11.5; F(1, 16) = 0.14, p = ns) kapa ka mor'a ho fokotsa boima ba 'mele (2-h sehlopha se nang le mafura a letsatsi le letsatsi: 22.4 s ± 7.0; Sehlopha sa mafura a monate: 16.5 ± 7.8; F(1, 16) = 0.32, p = ns). Ha ho etsoa liteko tsa ho etsa lintho tse tloaelehileng, ka bobeli bo tloaelehileng le ho fokotsa boima ba 'mele, ho ne ho se na phapang e khōlō pakeng tsa ratsana tsa 2-h tsa Litlolo tsa Mafura le Li-Acate Sweet-Fat ka mokhoa oa ho etsa lintho tse ntle (Feie. 4).

Setšoantšo sa 4 

Exp. 4: Kakaretso ea ho koetlisa e na le lintlha tsa ho fokotsa boima ba 'mele pele le ka morao (ho bolela ± SEM). Ho sa tsotellehe sehlopha, likarabo tsohle li ne li sebetsa ka matla boima ba 'mele bo fokotsehang ho feta pele ho lahleheloa ke boima ba' mele, *p <0.05.

Ha boima ba 'mele bo fokotsehile, ho sa tsotellehe sehlopha, likokoanyana kaofela li ne li sebetsa haholoanyane (F(1, 16) = 7.13, p <0.05, Feie. 4) mme a qeta nako e eketsehileng bohareng (F(1, 16) = 11.83, p <0.005; 2-h Mafura a Monate a Letsatsi le Letsatsi: 12.0 ± 1.7 mets ho fokotsa boima ba 'mele, ho fapana le 9.6 ± 1.6 min ka boima bo tloaelehileng; Fat-Sweet Acute: 12.8 ± 3.2 min ho fokotsa boima ba 'mele ha ho bapisoa le 8.8 ± 2.2 min ho boima bo tloaelehileng ba' mele) ea kamore ea ts'ebetso ea locomotor ha e bapisoa le boits'oaro ba bona ka boima ba 'mele bo tloaelehileng, empa ho ne ho se tšebelisano lipakeng tsa boima ba' mele le sehlopha.

Puisano

Ho itšetlehile ka se fumanoeng ke liteko tsena tse 'nè, litoeba li ja lijo tse monate tse nang le mafura le tsoekere ha lia ka tsa bontša matšoao a mangata a naxone-precipitated kapa a ikemetseng opiate-like ho tlosoa. Ho fanoe ka liphuputso tse fetileng tseo likhohlo li li jang lijong tsa ho ja lijo tse tsoekere tsa tsoekere [] (e neng e boetse e hlalositsoe mona ho Exp. 3), re ne re lebeletse litoeba tse nang le inxone tse nang le phihlelo e fokolang, e nang le mafura a mangata ho bontša matšoao a tšoanang a ho tlohela. Leha ho le joalo, ho kenngoa ha mafura a ho ja ho ka 'na ha kena-kenana le polelo ea lipontšo tsa ho tlohela. Ka hona, liphuputso tsena li fana ka maikutlo a hore ho tlosoa ha opiate-joaloka ho tlosoa ha lijo ha hoa hlokomeloa ka lebaka la ho ja lijo tse ngata tse utloisang bohloko, haholo-holo ba ruileng mafura, e leng, joaloka tsoekere, tse tsejoang ho etsa liphello mokhoeng opioid ea boko. Ka hona, ho hlaha ha lipontšo tsa opiate-joaloka ho khaotsa ho bonahala e le ho arabela ka ho ja lijo tse tlatsetsang ho bonahala eka ho na le mefuta e mengata ea lik'hemik'hale.

Lijo tsa Addictive tsa Lijo tse Phahameng ka Fat le Sugar

Litlhahlobo tse fetileng re hlalositse sephetho se tsoang ho laboratori ea rona le ba bang ba fana ka maikutlo a hore ho fihlella ho fokolang ho tsoekere ho ka fella ka matšoao a mangata a boitšoaro le a methapo ea ho lemalla lintlheng, ho akarelletsa le ho tlosoa ha opiate-like [, ]. Ho 'nile ha e-ba le lithuto tse sebelisang mefuta ea liphoofolo e bontšang hore ho fumana lijo tse nang le mafura le hona ho ka etsa hore ho be le matšoao a mang a ho lemala []. Sehlopha sa Corwin se bontšitse keketseho ea tsoelo-pele-likarabello tse arabelang likokoanyana tse jang mafura, li fana ka maikutlo a ho susumetsa mohopolo []. Bale le basebetsi-'moho le bona ba bontša hore litoeba tse bolokiloeng lijong tse ngata tse mafura kapa tse nang le lik'habohaedreite ebe li hana ho fumana lijo li tla mamella ho tsosoa ha mohopolo e le hore li fumane lijo tse lakatsehang []. Ka mor'a nako ea ho tlohela ka thata (likhohlano), litoeba tse nang le ho ja lijo tse ngata li bontša matšoenyeho hammoho le pontšo e fokotsehileng ea motsoako oa corticotropin mokokotlong oa amygdala. Leha ho le joalo, McGee le basebetsi-'moho ha ba bone matšoao a ho ba le khatello kapa tšusumetso e matlafatsang ho sebelisa kemiso ea karolelano e tsoelang pele ka mor'a ho lahleheloa ke phihlelo e fokolang ea letsatsi le leng le le leng ho khutsufatsa meroho e monate, e tšoanang le lijo tseo re li sebelisang Exp. 2 []. Ka kakaretso, lipatlisiso tsena li bontša hore matšoao a itseng a ho lemala a ka hlahisoa ha liphoofolo li fanoa ka lijo tse nang le mafura, empa liphello li rarahaneng mme li ka susumetsoa ke maemo a kang ho entsoe ka lijo, boima ba 'mele le kemiso ea ho fihlella.

Tlhaloso ea Macronutrient, Fomu le Boemo ba Lintho tse Phelang Lijo Tse Tšoanelang

Liphuputso tsa morao-rao li kenyeletse mefuta e sa tšoaneng ea lijo tsa mafura, ho kenyeletsa tse ling tse phelisang hantle, tse tšoanang le "lijo." Tse ling li ne li tlatsana le lijo tse tloaelehileng tsa lijo, tse tšoanang le "lijo tse hlahisang lijo," tse atisang ho sebelisoa nakong ea li-epidemic []. Lijo li ne li boetse li fapane ka tsela ea tlhaho, ho tloha lijong tsa pellet ho Exp. 1, phepo ea lijo tse matla-thata e Exp. 2 le lijo tsa metsi ka Exp. 3. Lijo tsa metsi li ne li sebelisoa ka lebaka la kamano e neng e tsejoa pele ho feta ho feta ho ja lijo tse ngata tsa metsi le phaello e latelang ea boima [, ]. Hape, hobane lipatlisiso tsa rona tsa pele li bontša matšoao a ho tlosoa ha opiate-joaloka ho khaotsa ho fihlella ho sebelisoa tharollo ea sucrose (e hlalositsoeng mona Exp. 3 moo liphoofolo li itlopa ho ja li-sucrose li qetile nako e fokolang letsohong le bulehileng la maze le ho bontša matšoao a ho tlohela ho etsa hore motho a se ke a hlola a e-na le bolokolohi boemong bo sabaletseng. Re ile ra leka mafura a metsi ho bona hore na mofuta oa lijo o ka ba le phello efe ea polelo ea mekhoa e amanang le ho itokolla. Leha ho le joalo, ho kena mokelikeli o nang le mafura ha hoa ka ha thibela matšoao a ho tlohela. Ho tsoa ho mefuta ena e fapaneng ea lijo tsa motsoako le sebōpeho, re etsa qeto ea hore ho sa tsotellehe mofuta oa lijo tse nang le mafura a mafura kapa mokhoa o fanoeng ka oona, liteko tsa hona joale ha lia ka tsa bontša matšoao a hlakileng a ho tlosoa ha opiate-joaloka ho tlosoa ha liphoofolo tse nang le ho finyella mafura.

Tlhahiso e 'ngoe e nkiloeng tlalehong ena e ne e le nako ea ho fihla. Tse ling tsa likhoto li ile tsa fuoa 12-h letsatsi le leng le le leng ho fumana lijo tse monate, ha ba bang ba fuoa phihlelo ea 2-h lenaneong la letsatsi le letsatsi kapa la nakoana. Mefuta e 'meli ea phihlelo e thibetsoeng e bontšitsoe ho fokotsa boitšoaro ba ho itlopa joala [, ]. Ho sebelisoa joala ho 'nile ha bontšoa hore ho na le liphetoho mekhoeng ea boipheliso ea boko, haholo-holo tsamaiso ea dopamine, ho batho ba babeli [] le mefuteng ea likhomo, tse tšoanang le liphello tse bonoeng ka lithethefatsi tse ling tsa tlhekefetso []. Le hoja lipampiri tsena tsa ho fihlela li bontšitsoe ho lebisa ho ho ja lijo tse ngata, tse ileng tsa netefatsoa litsing tsa hona joale, ha ho le nako ea ho fumana liteko e lekiloeng e lebisitseng matšoao a kang opioid ea ho tlohela mafura.

Tlhaloso ea Lipatlisiso Tse Nts'etsing Mekhoeng ea Kajeno

Le hoja ka kakaretso, data e bontša hore matšoao a ho tlosoa ha opiate-joaloka ha a hlahelle ha likhoto li fanoa ka ho fokotsa lijo tse nang le mafura a nang le mafura, ho na le lintho tse ntle tse fumanoang mohloling oa liteko o lumellanang. Ho Exp. 1, ka mor'a 46 h ea ho tlosoa ho phoka e monate, likhofu tseo pele li neng li e-na le 2 h li fihlella li bonts'itse maemo a seng makae a ho tšela ka mahlakoreng ha a bapisoa le ad libitum lisebelisuoa tse fepehileng (standard rodent chow kapa mafura a phahameng, a monate rodent chow). Ho ba le tšusumetso e matla ho 'nile ha hlokomeloa nakong ea k'hok'heine ho tlosoa ka litoeba []. Leha ho le joalo, ha ho na matšoao a ho tlosoa ha opiate-joaloka tse ling tse ileng tsa etsoa sehlopheng sena, tse kang litekanyetso tsa somatic tsa ho tlosoa.

Ho Exp. 2, ka mor'a 24 h ea liphoofolo tse amohelang batho ad libitum ho fumana lijo tse monate o monate ho bontšitse ho fokotseha nako eo ue qetileng ka letsoho le bulehileng la maze le ho feta. Tlhaloso ena e thahasellisa, kaha e bontša hore sehlopha se na le ad libitum ho fumana lijo tse monate ho ile ha bontša phetoho boitšoarong bo amanang le ho tlohela. Leha ho le joalo, ha e lekoa ho 36 h, phello e ne e se e sa bonahale. Sena se ka ba ka lebaka la hore ho na le nako e itseng ea nako eo ka eona matšoao a matšoenyeho a hlahelang, 'me nako eo e felile ka nako e latelang ea tekanyetso. Kapa, ​​ho ka fana ka maikutlo a hore ho sebelisoa ha maze e holimo ho feta ho ile ha fetola mokhoa oa teko. Le hoja liphuputso tse ling li bontša hore ho pepesehela khafetsa molekong o phahameng le ho feta ha ho ama phello ea teko [, ], ba bang ba tlaleha mokhoa oa tloaelo [-]. Sebopeho sa hona joale sa boholo-holo, karolo e khōlō ha ho na ho se tšoane ho ileng ha bonoa pakeng tsa lihlopha tse nang le matšoenyeho, e leng se ka bontšang hore ha ho na phapang e bakoang ke ho pepeseloa khafetsa. Leha ho le joalo, tse ntle le ad libitum-fats'e liphoofolo ka Exp. 2 e lokela ho nkoa ho latela taba ea ho sebelisoa ha tlhahlobo ena khafetsa.

Karolo ea Boima ba 'Mele ka Pontšo ea Matšoao a Bokhoba

Thupong ea hona joale, re ile ra hlahloba mefuta e fapaneng ea ho ja joala le boima ba 'mele, tseo ka bobeli li bontšitsoeng hore li kenya letsoho ho matšoao a kang ho lemalla lithethefatsi. Lihlopha tse ling li bontšitse hore ha likhoto li fuoe ho fokotsa ho ja lijo tse monate, tsa tsokolate, li fetoha bobebe ebile li bontša boitšoaro bo kang ba anxiogenic ha li haneloa ho fumana lijo tse monate []. Lipatlisiso tsa rona tsa pele li bontša mokhoa oa ho itokolla-o kang oa liphoofolo tse bolokiloeng ka li-intermittent sucrose, boima bo tloaelehileng. Liphuputso tse ling li bontšitse hore liphoofolo tse mafura li na le ad libitum kapa ho ba le monyetla o fokolang oa mokhoa oa ho ja lijo tsa mokhoa oa ho ja lijo tsa motsoako oa disolimbic dopamine neurotransmission [, ], empa liphoofolo tse nang le mokhoa o thibetsoeng (ke hore, ho itlosa bolutu) tse neng li sa khetholloe e le li-obese ha lia ka tsa bontša li-receptor tsa dopamine tse fokolang fatše. Sena se totobatsa khopolo ea hore botenya ka boeona bo ka lebisa liphetohong tsamaisong ea boko ba boko []. Ka lehlakoreng le leng, liphuputso tsa batho ba nang le ho itlopa joala li bontša hore ho itlopa joala, ho se na botenya haholo, ho baka liphello tsa tsamaiso ea DA [], e leng ho totobatsang bohlokoa ba ho ithuta mefuta e tobileng ea ho ja ho tlōla le botenya, ka bobeli hammoho le ka boithatelo. Ka pampiri e teng hona joale, ha rea ​​ka ra bona matšoao a ho tlohela opiate-joaloka ho tsoa likokoanyana tse ileng tsa fetoha boima bo feteletseng ka lijo tse nang le mafura (Exp.1). Hobane liphuputso tsa pele li bontša hore botenya bo ka fokotsa liphetoho tse kang tsa ho lemalla boko, tse ka 'na tsa e-ba le likarolo tse kang ho khaotsa ho ipolaea, ho ka etsahala hore ebe re khonne ho sheba mefuta e sa tšoaneng (ke hore, ho se na opiate) matšoao a ho tlohela lintlheng tsena.

Ho Exp. 4 re ile ra hlahloba phello ea ho fokotsa boima ba 'mele ha ho hlaha matšoao a ho tlohela. Li-rats tse nang le histori ea ho hlekefetsa li fumana li-cocaine ka potlako ho itšetlehile ka litsamaiso [], 'me ho bontšitsoe palo ea boima ba' mele ho ntlafatsa liphello tsa moputso oa lithethefatsi []. Ho fokotsa litebelisoa tsa likhoto ho fella ka ho fokotseha ha maemo a DA ho NAc ho 33% ea litekanyetso tsa motheo [, ]. Re kile ra fumana hore ha 'mele oa boima ba likhoto o nang le histori ea ho ja lijo tse tsoekere e fokotsehile ho fokotsoa ho 85%, ho lokolloa ha DA ho arabela tsoekere ho eketseha []. Bakeng sa mabaka ana, re ne re nahana hore ho fokotsa litekanyo tsa 'mele oa litsi ho ka ntlafatsa pontšo ea matšoao a ho tlohela. Leha ho le joalo, ho Exp. 4, li-naxone-precipitated signs of withdrawal ha lia ka tsa hlokomeloa ha likhofu li lahleheloa ho 85% ea boima ba 'mele ba bona bo tloaelehileng.

Joaloka tekanyo e eketsehileng ea matšoenyeho, re ile ra hlahloba mosebetsi oa ho lokisa. Mosebetsi oa ho holisa o eketsehileng o amahanngoa le ho tlosoa ha lithethefatsi [-], 'me e fumanoe ho Exp. 3 likokoanyana li ja lijo tse tsoekere, empa ha li ratsane tse nang le mafura a fokolang. Ho feta moo, ka Exp. 4, ho ne ho se na phapang e khōlō pakeng tsa likhoho tse jang mafura le li-rats ka likhoka, ka bobeli kapa bo fokotsing boima ba 'mele.

fihlela qeto e

Likokoana tse bolokiloeng ka ho ja lijo tse nang le ho ja lijo tse nang le tsoekere le mafura ha lia ka tsa bontša matšoao a ho tlosoa ha opiate-joaloka ho tlosoa ho feta tekano, boima bo tloaelehileng kapa boima bo tlaase, ho sebelisa mefuta e meholo e tiileng le ea metsi. Liphetho tsena li fapana le liphuputso tse fetileng tsa laboratori ena, le tse ling, tse bontšang boitšoaro bo tšoanang le ba opiate-ho tlohela likokoanyana tse jang tsoekere. Liphuputso tse teng hona joale li tšehetsa khopolo ea hore matšoao a ho lemala ha a arabela lijo tse matlafatsang e ka 'na ea e-ba limatlafatsi tse itseng, a totobatsa bohlokoa ba ho tsoela pele ho batlisisa phapang ea phapang eo ho ja lijo tse ngata tse nang le limatlafatsi ho ka ba le mekhoa ea ho fumana melemo ea boko.

​ 

Lintlha-khōlō tsa Patlisiso

  • Liphuputso li bontša mekhoa ea methapo ea maikutlo le ea boitšoaro ea ho lemalla ha liphoofolo li ja lijo tse nang le mafura a mafura.
  • Ho tlosoa ha li-naloxone-precipitated ha hoa ka ha bonoa ke likhoto tse jang lijo tse jang lijong tse ngata tse mafura, tse monate.
  • Ho tlosoa ha motho ho tsoa moeeng ho ne ho sa bonoe ke likhoto tse jang lijo tse jang lihlahisoa tse fapaneng tsa mafura, tse monate.
  • Ho fokotsa boima ba 'mele, bo tsejoang hore bo ka etsa hore ho be le liphello tse mpe tsa tšebeliso e mpe ea tlhekefetso, ha hoa ka ha ama matšoao a nang le nangxone-a thibelang ho tlosoa ha opiate.
  • Li-rats tse tloaelehileng tsa ho ja lihlahisoa tse mafura ha li bontše matšoao a ho tlosoa ha opiate-joaloka tlas'a maemo a sebelisoang.

lumela hore baa fokola

Phuputso e ne e tšehetsoa ke thuso ea USPHS AA-12882 (BGH) le DK-079793 le National Eating Disorders Foundation (NMA).

Mongolo o botlaaseng ba leqephe

 

Boitlhotlhollo ba Mohoeletsi: Ena ke faele ea PDF ea mongolo o ngotsoeng ka letsoho o sa amoheloang o amoheletsoeng bakeng sa ho hatisoa. Joaloka tšebeletso ho bareki ba rona re fana ka phetolelo ena ea pele ea mongolo o ngotsoeng ka letsoho. Mongolo o ngotsoeng ka letsoho o tla ba le ho kopitsa, ho kenya lihlopha le ho hlahloba bopaki bo hlahang pele o hatisoa ka mokhoa oa oona oa ho qetela. Ka kopo hlokomela hore nakong ea mekhoa ea tlhahiso ea lihlahisoa e ka fumanoa e ka amang litaba, le litsebiso tsohle tsa molao tse sebetsang koranteng e amanang le eona.

 

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