Kusokonezeka kwa mesolimbic dopamine kupatsirana kwa kakompyuta zakudya zowonongeka (2009)

Ndemanga: Kafukufuku akuwonetsa kuti kudya kwambiri "chakudya chodyera" kunenepa kwambiri kumabweretsa kuchepa kwa milingo ya dopamine ndikuwongolera kuyankha kwa dopamine ku makoswe wamba chow. Komabe, makoswewo adalandirabe mphotho pazakudya zodyeramo. Chimodzi mwamafukufuku omwe akuwonetsa kusintha kwamaubongo ofanana ndi omwe amamwa mankhwala osokoneza bongo. Kugwiritsa ntchito mphotho zachilengedwe mopitirira muyeso kumatha kubweretsa chizolowezi.

Neuroscience. 2009 Apr 10; 159 (4): 1193-9. yani: 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 ndi EN Pothosa,*

Mtundu womaliza wa chosindikiza wa nkhaniyi ukupezeka pa Neuroscience

Onani zina mwa PMC zomwe anatchulapo nkhani yosindikizidwa.

Pitani ku:

Kudalirika

Kuwonjezeka kwamtundu wa caloriki mu zakudya zowonjezera kwambiri kungayendetsedwe ndi njira zofunikira zomwe zimayendera khalidwe lofunafuna mphoto. Masolimbic dopamine dongosolo, ndipo phokoso limagwiritsidwa ntchito makamaka, limapereka mphoto kwa zakudya ndi mankhwala. Tinafufuza ngati chakudya cha makoswe chokwanira chikugwirizana ndi kusintha kwa dopaminergic neurotransmission m'dera limenelo. Nkhumba-Dawley makoswe anayikidwa pa zakudya zodyera kuti apangitse kunenepa kwambiri kapena chakudya cha laboratory chow kuti akhalebe olemera. Maselo a extracellular dopamine anayesedwa ndi mu vivo kusanthula kwazing'ono. Kutulutsa kwa dopamine pamagetsi kunayesedwa ex vivo mu magawo am'magazi a nucleus accumbens ndi dorsal striatum pogwiritsa ntchito nthawi yeniyeni ya kaboni fiber amperometry. Kupitilira masabata a 15, makoswe odyetsa odyera adayamba kunenepa kwambiri (> 20% akuwonjezeka thupi) ndikuwonetsa ma cell ochepa omwe amaphatikizira ma dopamine kuposa makoswe wamba (0.007 ± 0.001 vs. 0.023 ± 0.002 pmol / nyemba; P<0.05). Kutulutsidwa kwa Dopamine mu nyukiliya yomwe imakhala ndi makoswe onenepa kwambiri kudalimbikitsidwa ndi vuto la kudya, koma sikunayankhe pakudya kwa labotale. Kulamulira kwa d-amphetamine (1.5 mg / kg ip) inavombenso yankho lomveka la dopamine mu makoswe ovuta kwambiri. Zizindikiro zomwe zimagwiritsidwa ntchito mothandizidwa ndi magetsi kuchokera ku dopamine signal ex vivo mu nucleus accumbens magawo zinawonetsa kuchepa kwakukulu kwa zinyama zazikulu (12 vs. 25 × 106 ma molekyulu a dopamine pachitonthozo, P<0.05). Zotsatira zikuwonetsa kuti kuchepa kwa mesolimbic dopamine neurotransication kumalumikizidwa ndi kunenepa kwambiri. Kutulutsa kwachisoni kwa dopamine kumatha kubweretsa nyama zonenepa kubweza ngongole pakudya chakudya chokoma "chotonthoza", cholimbikitsa chomwe chimatulutsa dopamine pomwe lab chow idalephera.

Keywords: nucleus accumbens, striatum, kudya, thupi, amphetamine, hyperphagia

Kuwonjezeka kofulumira kwa chakudya chambiri m'mayiko otukuka kukuwonetsa kuti njira zopanda mphamvu zapakhomo zomwe zimapangitsa kuti thupi likhale ndi mphamvu zowonjezera zitha kukhala ndi udindo. Funso lofunika kwambiri ndilo chifukwa zinyama zamatera ndi anthu amapitirizabe kudya chakudya chopatsa mphamvu, chopatsa thanzi mpaka kufika poti zimakhala zobiriwira. Kuchokera ku lingaliro la chisinthiko, ziyenera kuyembekezera kuti ubongo unapanga dongosolo kuti liyankhule ndi mphotho zachilengedwe, monga chakudya. Njirazi zimagwiritsidwa ntchito pamtundu uliwonse kuti zitheke kuti apulumuke (Kelley ndi Berridge, 2002) ndipo amatha kuyanjana kapena kuwonetsa maulendo omwe amayendetsa kulemera kwa thupi. Choncho, kupezeka kwa chakudya chopatsa thanzi chopatsa thanzi kungachititse kuwonjezereka kwa caloric ndi kulemera kwapamwamba kuti njira zogwiritsira ntchito homeostasis, zomwe zimayambira makamaka mu hypothalamus, sizingagonjetsedwe. Izi zingathe kufotokozera, mwina mbali imodzi, mliriwu kuchuluka kwa chakudya chokwanira.

Makamaka pakati pa neural systems ndi masolimbic dopamine njira, kumene zochita za dopamine, makamaka mu nucleus accumbens terminals, zimadziwika kuti zimathera njira zowonjezera. Kutsegulira kwa dongosolo lino kumaphatikizapo kukwera kwa ma dopamine ndi kusintha kwa dopamine chibadwidwe pambuyo pochita zachilengedwe zokondweretsa monga kudyetsa (Hernandez ndi Hoebel, 1988; Radhakishun et al., 1988). Kuonjezera apo, dopamine mu nucleus accumbens (ndi pafupi ndi dorsal striatum) amadziwika kuti ikuwonjezeka ndi kuwonetsa zosokoneza zomwe zimakhudzana ndi zakudya zokhudzana ndi kupeza chakudya (Mogenson ndi Wu, 1982; Bradberry et al., 1991; Salamone et al., 1991). Choncho, ndizomveka kuyembekezera kuti kunenepa kwambiri kumagwirizanitsa ndi manolimbic dopamine-kutulutsa mphamvu ya chakudya chopatsa mphamvu kwambiri.

Mu phunziro ili, tafufuza ngati kutuluka kosatha (masabata a 15) a makoswe ku chakudya chokwanira, chopatsa thanzi chopatsa thanzi kumapangitsa kusintha kwa nucleus accumbens dopamine. Zakudya zabwino kwambirizi zimapangitsa kuti anthu azidya kwambiri m'kamwa ndipo amathandiza kwambiri kuti munthu azikhala wochuluka kwambiri (Sclafani ndi Springer, 1976). Kuwonjezera pamenepo, chakudya chodyera chimatipatsa kusiyana pakati pa zokonda kwambiri zamtundu wa mafuta ndi zakuthambo komanso ngati zoterezi zinakhudza masolimbic dopamine kumasulidwa. Tapeza kuti makoswe a Sprague-Dawley adatenga zakudya zambiri zamtundu wa tsiku ndi tsiku kuchokera ku magwero apamwamba kwambiri a kagawodidi ndipo adayambitsa kunenepa kwambiri kwa zakudya (DIO). Kuwonjezera apo, iwo anasonyeza kuvutika maganizo kwa basal dopamine kumasulidwa mu nucleus accumbens ndi attenuated response dopamine ku standard standard chow chakudya kapena systemic administration of d-amphetamine.

NJIRA ZOFUNIKA KWAMBIRI

nyama

Amayi aakazi Amagazi-Dawley makoswe (Taconic, Hudson, NY, USA), amafananitsidwa ndi kulemera kwa 300 g aliyense ali ndi zaka za 3. Zinyama zazimuna zidasankhidwa chifukwa, posiyana ndi makoswe aamuna, kulemera kwa thupi la ma laboratory-chow anadyetsa akazi ndikokhazikika pa nthawi. Nyama zinkaikidwa payekha m'chipinda chimodzi pansi pa kuwala kwa 12-h kutsogolo / mdima (kuwala pa: 6 pm, kuyatsa: 6 am). Pansi pa zochitikazi sitinawonongepo mbali ya estrous mkombero gawo pa mesolimbic dopamine kumasulidwa (Geiger et al., 2008). Zinyama zonse zinagwiritsidwa ntchito motsatira ndondomeko yofalitsidwa ya US National Institutes of Health (NIH) ndi Institute Institutional Animal Care and Use (IACUC) ya Tufts University ndi Tufts Medical Center. Khama lonse linayesedwa kuchepetsa chiwerengero cha zinyama zomwe amagwiritsidwa ntchito pofuna kuchepetsa kugwiritsira ntchito ziweto ndi kuvutika.

Zakudya zopangira chakudya

Nyama zinagawidwa kukhala chakudya cha DIO gulu (lomwe limafotokozedwanso kuti ndilo zakudya zopatsa thanzi pansipa) ndi gulu la odyera la ma laboratory (gulu lolemera labwino). Magulu onse adadyetsedwa ad libitum. Chakudya chodyetserako chakudya chinali ndi zigawo zamtengo wapatali monga Crisco (33% masamba yofupikitsa, 67% Purina powder), salami, cheddar tchizi ndi batala wamkonde; ndi zigawo zapamwamba zamaguludidi monga mkaka wosungunuka mkaka (Magnolia mtundu wosakanizidwa ndi madzi, 1: 1), chokoleti chipukhuki, chokoleti cha mkaka, nthochi, marshmallows ndi 32% sucrose yankho. Zakudya zabwino kwambirizi zakhala zikuwonetseratu kuti zimathandiza kwambiri kuti anthu azidya kwambiri m'kamwa ndipo amatsanzira kukula kwa kunenepa kwaumunthu (Sclafani ndi Springer, 1976). Chigawo chilichonse chinalipo nthawi zonse ndipo chinasintha kanayi pamlungu. Gulu la chakudya cha DIO, kuphatikizapo chakudya chokoma, chinaperekedwanso ad libitum Kufikira ku laboratory ya Purina chow. Kuti mudziwe zakudya zamagulu, kudya kwa chigawo chilichonse cha zakudya zodyerako kunayesedwa pa nthawi ziwiri za 48-h pa sabata la khumi ndi limodzi la chakudya. Zolemera za thupi zinalembedwa kamodzi sabata iliyonse.

Opaleshoni ya Stereotaxic

Opaleshoni ya Stereotaxic inkachitika pamapeto a 7 ya phunziroli (n= Chakudya cha 24 makoswe a DIO, n= Amphaka a chow a 32). Nyama zinkasakanizidwa ndi ketamine (60 mg / kg ip) ndi xylazine (10 mg / kg ip) pofuna kukhazikitsidwa kwa 10 mm, 21 gauge-steel steel microdialysis chingwe cannulas chomwe chimagwiritsidwa ntchito pamtunda wa posterior womwe umapezeka m'dera la chipolopolo. The stereotaxic ikugwirizana ndi 10 mm kutsogolo kwa interaural zero, 1.2 mm patsogolo mpaka sinusus sinus ndi 4 mm ventral mpaka phazi lachangu pamwamba. Pulogalamu ya dialysis yowonongeka inapanga china 4 mm ventral kuti ifike kumalo osokoneza (Paxinos ndi Watson, 2007). Pambuyo pa opaleshoni, zinyama zonse zinabwereranso ku malo osungirako katundu ndipo zinapitiliza pa zakudya zawo.

Microdialysis ndi njira yabwino kwambiri yogwiritsira ntchito mankhwala a chromatography (electrochemical detection) (HPLC-EC)

Microdialysis inkachitika patsiku la 14 la phunzirolo kuti lilolere kuchipatala chokwanira. Pazilombo zonse za microdialysis zinayikidwa payekha muzitsulo za microdialysis ndi machulukidwe zinaikidwa mu microdialysis cannulas 12-15 h isanathe kusonkhanitsa. Malo obwezeretsa (kumanzere kumanja) anali counterbalanced. Mapulogalamu a Microdialysis anali a mitundu yosiyanasiyana, yomwe inkapangidwa kumaloko ndipo adawonetsa 10% kuyambiranso kwa mankhwala a m'magazi. mu m'galasi mayesero monga tafotokozera kale (Hernandez et al., 1986). Ma probes anali opangidwa ndi mankhwala a Ringer (142 mM NaCl, 3.9 mM KCl, 1.2 mM CaCl2, 1.0 mM MgCl2, 1.4 mM Na2HPO4, 0.3 mM NaN2PO4) pa mlingo wa 1 ° μl / min. Dialysate inasonkhanitsidwa mu 40 μl mbale yomwe ili ndi 5 μl yodzitetezera (0.1 M HCl ndi 100 ° μM EDTA) kuti ichepetse kuyimitsidwa kwa monoamines. Kusonkhanitsa kwa zitsanzo kunayamba pakati pa mdima, ndipo chakudya chonse chinachotsedwa 3 h chisanachitike zitsanzo za zinyama zonse. Zitsanzo zinasonkhanitsidwa pa mphindi za 30 chifukwa chotsatira zochepa za 2 h zazitsulo, ndikutsatiridwa ndi dongosolo la dongosolo d-amphetamine (1.5 mg / kg ip; Sigma, St. Louis, MO, USA). Kuchokera muyeso iliyonse, 25 μl ya dialysate inalowetsedwa mu dongosolo la Antec HPLC-EC la amperometric (GBC, Inc., Boston, MA, USA) ndi khola la Rainin la 10 ndi chipangizo cha phosphate, chomwe chimasiyanitsa ndikuzindikira dopamine, ndi dopamine metabolites dihydroxyphenylacetic acid (DOPAC) ndi homovanillic acid (HVA). Zotsatira zazomwezi zinkawerengedwa ndi kulembedwa. Kuikidwa kwa kafukufuku wa microdialysis pamalo ochindunji kunatsimikiziridwa kumapeto kwa kuyesedwa kwa kafukufuku wake wa kafukufuku wa kafukufukuyu pambuyo pa kukhazikitsa ubongo ndi paraformaldehyde.

Zinyama zomwe zimapangidwa ndi chophimba cha ma laboratory cha 30 kapena chakudya cha zakudya m'malo mwa d-amphetamine, magulu onse anali osowa chakudya chifukwa cha 12 h pang'onopang'ono ndi microdialysis kuyesera kutsimikizira zokwanira kudya.

Kagawo kakang'ono ka magetsi

Ubongo wa makoswe unayikidwa mofulumira mu ayezi-ozizira mpweya wokhazikika wamadzimadzi (aCSF) pa Leica VT1000S vibratome (Leica Microsystems, Wetzlar, Germany), ndipo adadula mu 300 μm magawo amodzi. Kusamba kagawo kali ndi aCSF (124 mM NaCl, 2.0 mM KCl, 1.25 mM KH2PO4, 2.0 mM MgSO4, 25 mM NaHCO3, 1.0 mM CaCl2, 11 mM shuga, pH = 7.3). Pambuyo pa 1 h mu aCSF zidutswa zidatumizidwa ku chipinda chojambulira ndi kupaka kwa oxygenated aCSF kwa 1 ml / min pa 37 ° C. Mafakitale amtundu wamagetsi, 5 μm m'mimba mwake, ndi malo odulidwa mwatsopano anaikidwa mu nucleus accumbens shell kapena dorsal striatum ~ 50 μm mu chidutswa, ndi reference electrode (Ag / AgCl waya) atalowetsedwa mu a baths aCSF ndipo magetsi ku 700 mV (Axopatch 200 B, Axon Instruments Inc., Union City, CA, USA). Bipolar, waya wokhotakhota, makina osokoneza (waya wozungulira 0.005 mu: MS 303 / 3, Plastics One, Inc., Roanoke, VA, USA) anaikidwa mkati mwa 100-200 μm wa electrode ya carbon fiber. Pulogalamu ya 2 ms pa + 500 μA yomwe inkachitika nthawi zonse inali yoperekedwa ndi Isoflex stimulus isolator (AMPI, Inc., Jerusalem, Israel) yomwe inachititsa kuti munthu asinthe nthawi zonse (Model S88; Grass Technologies, West Warwick, RI, USA) . Yankho la electrode yamperometric (kusintha pa maziko oyambirira) linayang'aniridwa ndi kuwerengedwa ndi software Superscope (GW Instruments, Inc., Somerville, MA, USA). Ma electrode amalembedwa musanayambe kugwiritsa ntchito ndi maulendo a m'mbuyo-osasunthika (mafunde asanu amagwiritsidwa ntchito, 300 V / s, -400 ku + 1000 mV, polemba zojambulazo ndi zamkati ndi 10 μM dopamine). Mapiri a Amperometric adadziwika ngati zochitika zazikulu kuposa 3.5 × phokoso la rms la maziko. Kuphatikizira kwachitali chinali nthawi pakati pa (a) chiyambi choyambira chokhazikika kuchoka pa chiyambi kufika pa malo oyamba omwe anaposa cutoff ndi (b) malo oyamba a deta pamlingo waukulu wa matalikidwe omwe analembetsa mtengo wa ≤0 pA. The maximum amplitude (iMax) chochitikacho chinali mtengo wapamwamba pazochitikazo. Kuti mudziwe chiwerengero cha mamolekyu (N) atatulutsidwa, malipiro onse a chochitikacho pakati pa zolemba zoyambirirazo adatsimikiziridwa, ndipo chiwerengero cha mamolekyumu chikuyesedwa ndi chibale N= Q /nF, ndikuti Q ndi chiani, n chiwerengero cha ma electron chinaperekedwa pa molekyu, ndipo F ndi nthawi zonse Faraday (96,485 C payeso). Chiwerengerocho chinachokera pa kuganiza kwa magetsi awiri operekedwa ndi molekyulu yochuluka ya dopamine (Ciolkowski et al., 1994).

Zitsulo zamagetsi

DIO ya Cafeteria kapena makoswe ophimbidwa ndi ma laboratory (n= 11 / gulu) adalumikizidwa monga momwe adayeserako kale ndi ziphuphu za 1 mm za dorsal striatum ndi nucleus accumbens zidatengedwa kuchokera ku 300 μm magawo a ubongo. Nkhonyazo zinayambitsidwa ndi 40 mM KCl yankho la 3 min kuti atulutse dopamine. Maselo a extracellular dopamine ndiye anayesedwa pogwiritsa ntchito njira ya HPLC yomwe inanenedwa pamwambapa.

Kusanthula deta

Njira ziwiri za ANOVA (gulu × nthawi) ndi zochitika mobwerezabwereza ndi kufufuza kwa positi ya Fisher ngati momwe zinalili kuyigwiritsira ntchito pofufuza deta ya microdialysis. Njira imodzi ANOVA idagwiritsidwira ntchito pazoyezetsa zina zonse. Kwa zowonongeka kagawo, zotsatira zake zinachokera ku magawo asanu osiyana pa kagawo kamodzi kokha pamene ANOVA idathamanga. Zotsatira zimayesedwa ngati zowona ± zolakwitsa zenizeni za tanthauzo (SEM).

ZINTHU

Makoswe odyetsa zakudya amakhala ndi chakudya chokoma kwambiri

Nkhokwe za DIO zapamadzi zinkakonda kwambiri mkaka wokoma (74.4 ± 6.4 g; 241 ± 21 kcal) ndi 32% sucrose solution (31.4 ± 4.1 g; 40 ± 5 kcal) (Fanizo. 1A, B, F(9,127) = 116.9854, P<0.01). Kuphatikiza apo, nyamazi zidadya zochepa kwambiri za Purina chow (5.66 ± 1.02 g) poyerekeza ndi ziweto zodyetsa za lab (54.7 ± 2.3 g; F(1,27) = 419.681, P<0.01). Pambuyo pa masabata 14 pakudya zakudya, makoswe adapeza 53.7% ya kulemera kwawo koyamba mpaka kulemera komaliza kwa 444.9 ± 19.0 g. Pambuyo pa nthawi yomweyi, makoswe a chow labotale adafika pachimake pa 344.0 ± 10.8 (Fanizo la 2A).

Chith. 1 

Chakudya cha zakudya zakudya zakudya m'zakudya zomwe zimakonda kwambiri makoswe. Chiwerengero cha zakudya zopatsa thanzi mu magalamu (A) ndi kcal (B) pa nthawi ziwiri za 48-h pa sabata la 11 la zakudya za zakudya zimasonyeza kukonda mkaka wokoma ndi mankhwala a sucrose (kutanthauza ± SEM; ...
Chith. 2 

Basal, amphetamine- ndi ma laboratory chow-coreed-rooted accumuls dopamine miyeso akuchepetsedwa mu zakudya ovuta makoswe. (A) Kulemera kwa thupi la chakudya Chakudya cha DIO pa nthawi ya masabata a 14 chinali choposa kwambiri ...

Makoswe odyetsa zakudya ali ndi basal dopamine ndipo amachepetsanso amphetamine.

Pa sabata la 14 la phunzirolo, makoswe a DIO amawonetsa ma dopamine ochepa kwambiri omwe amapezeka pamtundu wa makoswe (0.007 ± 0.001 pmols / 25 μL chitsanzo vs 0.023 ± 0.002 pmols / 25 μL chitsanzo; Fanizo la 2B, F(1,19) = 11.205; P<0.01), monga momwe anayeza mu vivo microdialysis. Masewu oyambirira a dopamine metabolites, DOPAC ndi HVA, amapezedwanso kuti ndi otsika kwambiri mu makoswe a DIO. Maseŵera a DOPAC mu cafeteria DIO makoswe anali 3.13 ± 0.42 vs. XUMUM ± 8.53 pmol mu makoswe a laboratory chow (F(1,10) = 14.727, P<0.01). Mulingo wa HVA unali 1.0 ± 0.28 vs. 4.28 ± 0.33 pmol motsatana (F(1,20) = 6.931, P<0.05). Pambuyo pokhazikitsa maziko okhazikika a dopamine, makoswe adapatsidwa jekeseni wa 1.5 mg / kg ip wa amphetamine. Kutulutsidwa kwathunthu kwa milingo ya dopamine kunali kocheperako makoswe a DIO poyerekeza ndi ziweto zodyetsa chowotcha (Fanizo la 2B, F(9,162) = 2.659, P<0.01).

Makoswe odyetsa zakudya amatulutsa dopamine mu nucleus accumbens pamene akudya chakudya chokoma kwambiri, osati la laboratory chow

Fanizo la 2D akuwonetsa kuti kuchuluka kwa dopamine ya extracellular mu cafeteria DIO makoswe sanawonjezeretseke pozindikira chakudya cha laboratory chow. Nyama idya kudya pafupifupi 1.3 ± 0.4 g ya chow pa 30 min. Komabe, pamene gawo la ziwetozi (n= 8) kenako idyetsedwa zakudya zodyera kwa 30 min, dopamine yowonjezera 19.3% kuchokera ku 0.027 ± 0.003 ku 0.033 ± 0.004 pmols / 25 μL chitsanzo (F(11,187) = 8.757, P<0.05). Mulingo wa DOPAC udakulanso ndi 17.13% ± 6.14%. Mosiyana ndi izi, kuchuluka kwa dopamine mu nyama zophunzitsidwa ndi chowotcha chinawonjezeka ndi 51.10% ± 17.31% (F(7,119) = 3.902, P<0.05) 1 h pambuyo pa chakudya cha chow (nyama zimadya pafupifupi 5.7 ± 0.8 g, koposa nyama za DIO; F(1,33) = 26.459, P<0.01). Komabe, sitiyembekezera kuti chakudya chotsika chomwe nyama za DIO ndizomwe zimayambitsa kusowa kwa kutulutsidwa kwa dopamine munyamazi chifukwa chakudya chotsika mpaka 0.6 g akuti chalimbikitsa dopamine kumasulidwa mu ma nyukiliya omwe amakhala ndi makoswe (Martel ndi Fantino, 1996). Kuwonjezera pamenepo, kafukufuku wina wasonyeza kuti kusiyana kwa dopamine kumasulidwa sikunagwirizanitsidwe molingana ndi kuchuluka kwa zakudya zomwe zilipo, komabe zimakhudzidwa ndi zovuta zina monga chiwerengero cha zinyama, chilakolako ndi zotsatira zabwino za chakudya (Hoebel et al., 2007). Chakudya chodyera sichinaperekedwe ngati chovuta kwa nyama zoweta zopangidwa ndi ma laboratory chifukwa zinayenera kuyambitsa zotsatira zatsopano zomwe zingasokoneze kusiyana kulikonse ndi chakudya cha DIO nyama.

Dokotala wamatsitsimutso otulutsa dopamine amatetezedwa m'magulu akuluakulu a ubongo kuchokera ku makoswe odyera kwambiri

Fanizo la 3A imasonyeza zochitika zamakono zochokera ku nucleus accumbens zigawo zazing'ono zosiyana ndi makoswe odyera kwambiri (n= Kukula kwa 30 mu magawo asanu ndi awiri kutsutsana ndi 24 kukondweretsa mu magawo asanu motsatira). Nkhokwe za DIO zakudya zapamadzi zinkamasulidwa kutsekemera kwa dopamine kusiyana ndi makoswe opangidwa ndi ma laboratory (12 × 106± 4 × 106 vs 25 × 106± 6 × 106 molekyulu; Fanizo la 3B, F(1,52) = 2.1428, P<0.05). Kusiyanaku pakumasulidwa kwa dopamine kumawonetsa kuchepa kwa matalikidwe azinthu (5.16 ± 1.10 pA m'malo odyera makoswe a DIO vs. 7.06 ± 0.80 pA mu makoswe omwe amadyetsa chow; Fanizo la 3C, F(1,52) = 2.4472, P<0.05) ndi m'lifupi (2.45 ± 0.73 s mu malo odyera makoswe a DIO vs. 4.43 ± 0.70 s mu labotale omwe amadyetsa makoswe, Fanizo la 3D, F(1,52) = 3.851, P<0.05).

Chith. 3 

Kuchotsa dopamine kuchoka ku nucleus accumbens mu magawo a ubongo (A) Maimidwe ochokera kumtundu wa phokoso wambiri amakhala ndi magawo a nyama zoweta (pamwamba; n= Kukula kwa 30 mu magawo asanu ndi awiri) ndi zakudya Zakudya za DIO (pansi; n= Zosangalatsa za 24 ...

Chith. 4 amasonyeza kuti zikhalidwe zomwezo zinalipo mu magawo osokoneza bongo a makoswe odyera kwambiri. Maimidwe oimira a laboratory odyetsedwa (n= Kukula kwa 31 mu magawo asanu ndi awiri) ndi chakudya cha DIO (n= Kulimbikitsa kwa 15 mu magawo anayi) magulu amasonyezedwa Fanizo la 4A. Magetsi otsukidwa dopamine kuchokera ku striatum anali 0.8 × 106± 0.1 × 106 mu cafeteria DIO makoswe vs 44 × 106± 11 × 106 mamolekyu (Fanizo la 4B, F(1,45) = 6.0546, P<0.01) munyama zaku labotore zomwe zidadyetsedwa. Apanso izi zikuwonetsa kuchepa kwa matalikidwe onse azomwe zikuchitika (2.77 ± 0.42 vs. 9.20 ± 1.88 pA; F(1,45) = 7.8468, P<0.01) ndi m'lifupi (0.22 ± 0.03 vs. 5.90 ± 0.98 s; F(1,45) = 17.2823, P<= 0.01) mgulu lodyera la DIO (Fanizo la 4C, 4D).

Chith. 4 

Kuchotsa dopamine kumasulidwa kuchoka ku dorsal striatum mu magawo a ubongo. (A) Maimidwe ochokera ku zigawo zowawa za dorsal striatum zinyama zopsereza (pamwamba; n= Kukula kwa 31 mu magawo asanu ndi awiri) ndi zakudya Zakudya za DIO (pansi; n= Kusintha kwa 15 mkati ...

Potaziyamu-inachititsa kuti dopamine amasulidwe minofu ya tizilombo toyambitsa matenda imachepetsedwa mu nucleus accumbens ndi striatum ya makoswe odyera kwambiri

Maselo a extracellular akutsatira KCl kuyesedwa anayesedwa ndi HPLC-EC ndipo amasonyezedwa Chith. 5. Miyeso ya extracellular ya dopamine inali 0.16 ± 0.08 pmol / nyemba m'magulu oundana a zinyama zambiri (n= 10 micropunches) poyerekeza ndi 0.65 ± 0.23 pmol / sampuli mu tizilombo toyambitsa matenda kuchokera ku zinyama (n= Zipiringi za 11; Fanizo la 5A; F(1,19) = 4.1911, P<0.01). Ma extracellular dopamine mulingo anali 5.9 ± 1.7 pmol / nyemba mu ma striatal micropunches ochokera onenepa kwambiri (n= Makoswe a 8) ndi 11.3 ± 1.9 pmol / sampulo pamalo omwewo kuchokera ku ulamuliro (n= Makoswe a 11)Fanizo la 5B; F(1,17) = 7.5064, P<0.01).

Chith. 5 

Mazira a extracellular dopamine ochokera ku potaziyamu-omwe amachititsa tizilombo toyambitsa matenda. Ambiri a dopamine atulutsidwa kuchokera ku (A) nucleus accumbens (n= Mipiringi ya 11 kuchokera ku gulu lililonse) ndi (B) dorsal striatum (n= 8 micropunches kuchokera kovuta komanso n= 11 micropunches kuchokera ku machitidwe) ...

KUKANGANANI

Mu phunziro lino, makoswe adakula kwambiri podya chakudya chodyetserako zakudya ndi zokonda zakudya zapamwamba zamagulu. M'madera awo olemera kwambiri, anali ndi dopamine yochepa kwambiri ya dopamine komanso ya dopamine yomwe inalimbikitsa kapena amphetamine. Pofufuza pogwiritsira ntchito mankhwala osokoneza bongo, nyama zimagwira ntchito kuti zisunge ma dopamine mu nkhono yomwe ili pamtunda wina (Wise et al., 1995a,b; Ranaldi et al., 1999). Mu phunziro lino, "nthendayi" yogwiritsidwira ntchito ndi chakudya chokoma, kotero chochepa cha dopamine chodziwika bwino mu accumbens chimabweretsa kuwonjezeka kwa chakudya chokoma.

Makoswe amodzi anasonyezanso kuti dopamine amatsitsimutsa magetsi m'mitsempha ya ubongo ndi potassium-yomwe inalimbikitsa dopamine m'magulu a tizilombo toyambitsa matenda kuchokera ku nucleus accumbens ndi dorsal striatum. Chosowa chachikulu cha presynaptic mu dopamine exocytosis, kotero, chikuwonekera pa zakudya zowonjezera kwambiri chifukwa kuvutika maganizo kwa kutuluka kwa dopamine kulipo mu vivo, m'magazi a ubongo ovuta kwambiri komanso osakanikirana ndi ubongo wambirimbiri. Tinawona zotsatira zofananako mu chibadwa cha maonekedwe a kunenepa kwambiri. Mu chitsanzochi, mRNA ndi mapuloteni owonetsera olamulira a dopamine synthesis ndi exocytosis kuphatikizapo tyrosine hydroxylase ndi neuronal vesicular monoamine yotumiza (VMAT2) adachepetsedwa mu ventral tegmental area (VTA) dopamine neurons ya nyama zowonongeka (Geiger et al., 2008). Chinthu china choyambitsa kusinthika kwachisipanishi ndi kapangidwe ka plasma dopamine reuptake transporter, DAT. Mapulogalamu a electrophysiology maphunziro amatilola kusiyanitsa pakati pa kusiyana kwa dopamine release ndi reuptake kinetics. Kusiyanitsa kwa kukula kwa ziphuphu kumasonyeza kuti nyama zowonjezera zinyama zinyama zikhoza kukhala ndi zochepa zowononga kumasulidwa komanso kusintha kwa kubwezeretsanso chifukwa cha kusiyana kwa malo otetezeka a DAT transporter pa membrane ya plasma. Mu Zucker mafuta (fa / fa) makoswe, kuwonjezeka kwa mRNA magulu a DAT transporter awonetsedwa ku VTA (Figlewicz et al., 1998). Zomwe zingatheke kuti chiwerengero cha dopamine chikhale chokwanira chikugwirizana ndi kuchepa kwa dopamine chizindikiro mu makoswe a DIO mu phunziro lino.

Tiyenera kuzindikira kuti mphamvu ya amphetamine yotulutsa dopamine sinatetezedwe ndi nyama zowonongeka (peresenti ya peresenti isintha kuchoka payambira) ndipo izi zikhoza "kukonza" pamodzi ndi dopamine m'munsi momwe zimakhalira zinyama zowonjezera kuti zitha kupeza dopamine kutulutsa zovuta. Amphetamine ndi malo ochepa omwe amachititsa dopamine kuchoka ku vesicles kupita ku cytosol ndipo amachititsa kuwonjezeka kwa extracellular dopamine kupyolera pamsewu wodutsa (Sulzer ndi Rayport, 1990). Ngati pali vuto lalikulu m'madzi otchedwa dopamine vesicular, monga momwe zilili m'thupi la vMAT2 lopanda mbewa, jekeseni wa amphetamine pamtunduwu umapangitsa kuti pakhale njira yatsopano ya dopamine mu cytosol (Fon et al., 1997). Kuwonjezeka kwa amphetamine kwachangu kwa cytosolic dopamine kungathe kufotokozera kuwonjezereka kwa peresenti peresenti Kusintha kwa accumbens dopamine mu nyama zowonongeka zomwe zimapezeka m'zinthu zolemetsa zowonongeka ndipo zingathandizire kuti nyama zowonongeka zitheke kuwonetsa dopamine kutulutsa zizindikiro pamodzi ndi mankhwala osakanizika ochepa kwambiri ma dopamine mu accumbens.

Kodi ndi njira ziti zomwe zingagwirizane ndi vuto la presynaptic dopamine mu zinyama zazikulu ndi kuyendetsa zakudya zawo? Chiyanjano pakati pa zakudya zokonda chakudya ndi nthenda yomwe imapezeka ndi dopamine imasonyezedwa momveka bwino pamene yankho lopweteka la nyama zowonjezereka zimadya, koma osati chakudya chokoma. Zomwe tapeza zikugwirizana ndi ntchito yatsopano yomwe ikuwonetsa kuti DXAMUMX-receptor agonist (D1) receptor agonist imapangitsa kuti makoswe adye zakudya zabwino kwambiri (Cooper ndi Al-Naser, 2006). Kuonjezera apo, nucleus accumbens dopamine imayikidwa mu makoswe ophunzitsidwa kuti azisunga pa sucrose (Avena et al., 2008), kupititsa patsogolo kuthandizidwa kwa dopamine pakati pa zokonda chakudya chokoma chochuluka m'zakudya. Ife tawonetsa chosowa chapakati cha dopamine chomwe chinaperekedwa mu phunziro laposachedwapa mu zitsanzo zina za kunenepa kwambiri, kuphatikizapo ob / ob khola loperewera la leptin ndi makoswe omwenso amatha kunenepa kwambiri (Fulton et al., 2006; Geiger et al., 2008). Choncho, chizindikiro chimodzi chotheka chogwiritsira ntchito zakudya zopatsa mphamvu komanso kusungidwa kwa dopamine kungakhale leptin. Anthu omwe ali ndi vuto lobadwa la leptin, m'malo mwa leptin amachepetsa hyperphagia ndipo amachititsa kusintha kwa ventralum yawo pogwiritsa ntchito kuyang'ana kwa chakudya chokoma (Farooqi et al., 2007). Mu makoswe amasonyezanso kuti leptin imachepetsa kudziyang'anira kwa sucrose (Figlewicz et al., 2006, 2007). Zotsatira zina zotere monga ghrelin ndi orexin zasonyezedwanso kuti zikuphatikizidwa pa kukhazikitsidwa kwa midbrain ya dopamine system (Rada et al., 1998; Helm et al., 2003; Abizaid et al., 2006; Narita et al., 2006). Zingakhale zosangalatsa kupitiliza kufufuza ngati kusinthasintha kwa zakudya zowonjezera zinyama kumalo ovomerezeka a ma laboratory nthawi zonse zikanakhalabe ndi chakudya chokoma komanso zomwe zimakhudza dopamine mmalo mwake popanda kusintha kwa leptin, ghrelin kapena orexin ndi zina zokhudzana ndi chilakolako cha kudya.

POMALIZA

Pomalizira, zomwe anapeza mu phunziro lino zikusonyeza kuti masolimbic dopamine dongosolo limakhala ndi ntchito yofunikira kwambiri pa zakudya zakuthambo, hyperphagia komanso chifukwa chodya kwambiri. Nucleus accumbens ndi dorsal striatum dopaminergic neurotransmission akuvutika maganizo pa makoswe ovuta kwambiri. Zinyama zimatha kubwezeretsa pang'onopang'ono miyeso ya dopamine mwa kudya zakudya zogwira mtima kwambiri. Zotsatira izi zimasonyeza kuti kuyang'anitsitsa kotheratu kwa antiynaptic regulators ya masolimbic dopamine dongosolo ndi njira yodalirika yothetsera kunenepa kwambiri kwa zakudya.

Kuvomereza

Ntchitoyi inathandizidwa ndi DK065872 (ENP), F31 DA023760 (BMG, ENP), Smith Family Foundation Award of Excellence mu Biomedical Research (ENP) ndi P30 NS047243 (Tufts Center for Neuroscience Research).

achidule

  • aCSF
  • zojambula zowonjezera madzi
  • DAT
  • dopamine plasma membrane transporter
  • DIO
  • kudya kunenepa kwambiri
  • DOPAC
  • dihydroxyphenylacetic asidi
  • HPLC-EC
  • kutentha kwambiri kwa madzi ndi chithunzithunzi cha electrochemical
  • HVA
  • homovanillic asidi
  • VMAT2
  • neuronal vesicular monoamine wotumiza
  • VTA
  • malo amtunda

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