UKUHLOLA - Ubungqina boKulutha kweShukela: Ukuziphatha kunye ne-Neurochemical Effects of Intermittent Excessive Sugar Intake (2008)

UNicole M. Avena, UPedro Rada, yaye U-Bartley G. Hoebel^*

Ulwazi loMbhali ► Ulwazi lobunikazi kunye neelayisensi ►

Umbuzo wovavanyo wokuba ingaba iswekile ingaba yinto yokuxhatshazwa kwaye ikhokelela kuhlobo lwendalo lokulutha. "Ulukutya" lubonakala lubonakala lubalulekile ngenxa yokuba iindlela zobuchopho ezivele zaphendula kwimivuzo yendalo nazo zenziwa ngamachiza alikhoboka. Iswekile iyaphawuleka njengesixhobo esikhupha ii-opioids kunye ne-dopamine kwaye ngenxa yoko kunokulindeleka ukuba sibe namandla okulutha. Olu hlaziyo lushwankathela ubungqina bokuxhomekeka kweswekile kwimodeli yezilwanyana. Izinto ezine zokulutha ziyahlalutya. "Ukuluma", "ukurhoxa", "ukunqwenela" kunye nokunxibelelanisa iminqamlezo nganye inikwa iinkcazo zomsebenzi kwaye ibonakaliswe ngokuziphatha ngokungxengxezisa iswekile njengesixhasi. Ezi ndlela zokuziphatha ke ezinxulumene notshintsho lwe-neurochemical kwingqondo olwenzeka neziyobisi ezikhobokisayo. Uhlengahlengiso lwe-Neural lubandakanya utshintsho kwi-dopamine kunye ne-opioid receptor yokubopha, i-enkephalin mRNA expression kunye nokukhululwa kwe-dopamine kunye ne-acetylcholine kwi-nucleus accumbens. Ubungqina buxhasa i-hypothesis yokuba phantsi kweemeko ezithile amagundane anokuxhomekeka kwiswekile. Oku kunokuguqulela kwezinye iimeko zomntu njengoko kucetyisiwe loncwadi malunga nengxaki yokutya kunye nokukhuluphala.

Ukuxilisa

Iindlela zokuqonda ukuba likhoboka linokuhlelwa ngokwamaqela amathathu (Umbutho we-Psychiatric Association, i-2000, UKoob noLe Moal, i-1997). Eyokuqala, ukubambisa, ichazwa njengokunyuka kokutya kakhulu ngexesha elinye, ixesha eliqhelekileyo emva kokuyekiswa ngokuzithandela okanye ngokunyanzelwa. Ukufumana okwandisiweyo ngendlela ye-binges kunokubangelwa kukuziva zombini kunye nokunyamezelana kwiimpawu zepropathi yento yokuxhatshazwa eyenzeka ngokuhanjiswa okuphindaphindiweyo. Sensitization, ezichazwe kwiinkcukacha ezinkulu apha ngezantsi, kukwanda kokuphendula ngokukhawuleza kukhuthazo olunikezelweyo. unyamezelo Kukuncipha kancinci kokuphendula, ngokokuze into efunekayo ivelise isiphumo esifanayo (McSweeney et al., 2005). Zombini kucingelwa ukuba zinefuthe elinamandla, lokuqinisa elinamandla leziyobisi zokuxhatshazwa kwaye libalulekile ekuqaleni komjikelo weziyobisi kuba bobabini banokunyusa ukuphendula kunye nokutya (UKoob noLe Moal, i-2005).

Ukurhoxiswa

Iimpawu zokurhoxa ziye zibonakale xa into exhatshaziweyo ingasasebenzi okanye ibhlokiwe ngekhemikhali. Siza kuthetha ngokurhoxa malunga nokushenxiswa kwe-opiate, eneempawu ezichaziweyo ngokucacileyo (UMartin et al., 1963, Indlela et al., 1969). Ukuxhalaba kunokuchazwa ngokusebenzayo kwaye kulinganiswe kwizilwanyana usebenzisa i-maze ephezulu, apho izilwanyana ezixhalabileyo ziya kuthintela ukuchitha ixesha kwiingalo ezivulekileyo ze-maze (Ifayile et al., 2004). Olu vavanyo luye lwangqinwa ngokubanzi ngenxa yokuxhalaba ngokubanzi (Umlingane et al., 1985) kunye nexhala elibangelwa kukurhoxiswa kweziyobisi (Ifayile kunye noAndrews, 1991). Uxinzelelo lokuziphatha okubonakalayo kwizilwanyana nako ukungenelwa, ngaphandle kokubhekisa kwiimvakalelo, kusetyenziswa uvavanyo-lokunyanzelwa, olunamanyathelo okuzama ukuqubha ngokuhamba ngokuhamba emanziniI -HTMLolt et al., 1978). Xa iimpawu zokurhoxiswa kwe-opiate zichazwe ngokucacileyo nge-naloxone, iphakamisa ukuba ukungasebenzi kwe-opioid receptors kungunobangela. Xa iimpawu ezifanayo ziveliswa ngokuzenzekelayo ngexesha lokuthintela, umntu unokucinga ukuba kungenxa yokunqongophala kwenkqubo ethile ye-opioid.

Ukuthanda

Inqanaba lesithathu lokulutha, ukuthanda, kwenzeka xa intshukumisa iphuculwe, ngokufuthi emva kwexesha lokuthintela (UVanderschuren no-Everitt, i-2005, Weiss, 2005). "Ukunqwenela" kuhlala kungachazwa kakuhle igama elihlala lisetyenziswa ukuchaza umnqweno onamandla wokuzisebenzisa ngokwakho iziyobisi ebantwini (Ubulumko, 1988). Ukusilela kweligama elingcono, siya kusebenzisa igama elithi "ukunqwenela" njengoko kuchazwa yimizamo eyongezelelweyo yokufumana into yokuxhatshazwa okanye i-cues zayo ezinxulumene noko ngenxa yokukhoboka kunye nokuyeka. "Ukunqwenela" kuhlala kubhekisa kwisishukumiso esigqibeleleyo, esinokulinganiswa kusetyenziswa imeko yokusebenza. Ukuba ukungakhathali kwenza ukuba isilwanyana sonyuse kakhulu ucinezelo lwaso, umntu unokuthatha oku njengophawu lokunyusa amandla.

Sensitization

Ukongeza kule ndlela yokuqonda ingentla, indlela oziva ngayo uziphatha ucinga ukuba ungaphantsi kwemeko ethile yokuxhomekeka kwiziyobisi (Vanderschuren kunye neKalivas, i-2000). Uvakalelo lokuziphatha kakuhle kulinganiswa njengokunyuka kwendlela ekuphendulwa ngayo kulawulo lwechiza eliphindaphindiweyo. Umzekelo, emva kokuphindaphindiweyo kwethamo le-amphetamine elandelwa kukungakhathali, idosi yomceli mngeni, enefuthe elincinci okanye engenalo nefuthe kwizilwanyana ze-naïve, ibangela ukuphawulwa okubonakalayo (I-Antelman kunye neCaggiula, 1996, Gick et al., 1986). Izilwanyana ezivezwa kwinto enye zihlala zibonisa imvakalelo yokuwela, echazwa njengempendulo ye-locomotor kwisiyobisi okanye into eyahlukileyo. Ukubonakalisa imvakalelo ezinqamlezileyo kunokubonakaliswa kukuziphatha okuqinisekileyo (I-piazza et al., 1989). Izilwanyana ezenzelwa isiyobisi esinye kunokubonisa ukwanda kokufumana ichiza elahlukileyo. Ngamanye amagama, ichiza elinye lisebenza “njengendlela yokungena” kwelinye. Umzekelo, izilwanyana zenzelwa amphetamine ukubonisa ukunyuka okukhawulezayo kokutya i-cocaine (UFerrario kunye noRobinson, 2007), kunye nezilwanyana ezixhonyiweyo ukuba i-nicotine isebenzisa utywala obuninzi xa kuthelekiswa nezilwanyana ezingenamvakalelo (I-Blomqvist et al., 1996). Oku kuziphatha kucingelwa ukuba kwenzeka xa amachiza ahlukeneyo esenza ukuba i-neural circry efanayo, kwaye sisizathu sokuba uninzi lweeklinikhi lufune ukuyeka iziyobisi ngokupheleleyo njengesiqhelo kunyango.Ubulumko, 1988).

Umbuzo wokuqala ophendulwe kolu hlaziyo kukuba ingaba naziphi na iimpawu ezichaziweyo ngokuziphatha zokuxhomekeka kwento zinokufunyanwa ngokufikelela iswekile. Umbuzo wesibini uphonononga iinkqubo ze-neural ukufumanisa ukuba iswekile ingaba nayiphi na ifuthe njengechiza lokuxhatshazwa.

3.A. Dopamine

Kumiselwe kakuhle ukuba iziyobisi ezikhobokisayo zenza ukuba i-neurons ene-DA kwiindawo zobuchopho ziqhubele phambili ngenkqubo yokuziphatha. Oku kuboniswe kumachiza ahanjiswe ngokwenkqubo (I-Di Chiara kunye ne-Imperato, i-1988, URadhakishun et al., 1983), kunye namachiza enzakaliswe ngaphakathi okanye osulelweyo kwindawo leyo (UHernandez kunye noHoebel, 1988, Mifsud et al., 1989). Ukuqikelelwa kwe-mesolimbic ye-DA ukusuka kwindawo yecandelo le-venral (VTA) ukuya kwi-NAc kusoloko kunyanzeliswa kwimisebenzi yokuqinisa (Ubulumko kunye no-Bozarth, 1984). I-NAc ibalulekile kumacandelo 'omvuzo' kubandakanya ukufuna ukutya kunye nokomeleza ukufunda, ukukhuthaza, ukunyusa amandla kunye nokusayina utshintsho oluvuselelayo (I-Bassareo kunye ne-Di Chiara, i-1999, EBerridge noRobinson, i-1998, Salamone, 1992, Schultz et al., 1997, Ubulumko, 1988). Nasiphi na i-neurotransmitter ekhuthaza ngokuthe ngqo okanye ngokungathanga ngqo imizimba yeeseli ze-DA kwiVTA yomeleza ukuzilawula kwalapha ekhaya, kubandakanya ii-opioids ezifana ne-enkephalin (I-Glimcher et al., 1984), iipeptide ezingezizo-opioid ezifana ne-neurotensin (I-Glimcher et al., 1987) kunye neziyobisi ezininzi zokuphathwa gadalala (U-Bozarth kunye noWise, 1981, UGosa et al., 1985, McBride et al., 1999). Ezinye iziyobisi ziyasebenza nakwizikhululo ze-DA (I-Cheer et al., 2004, Mifsud et al., 1989, UNisell et al., 1994, U-Westerink et al., 1987, Yoshimoto et al., 1992). Ke ngoko, nayiphina into ebangela ukuba kukhululwe i-DA okanye inciphise ukuphinda kubuyiswe kwi-DA kwizikhululo ngezi setyhula inokuba ngumgqatswa wokuxhatshazwa.

Ukutya okuninzi okunokukhupha iDA kwi-NAc, kubandakanya i-lab chow, iswekile, isalcharin, kunye neoyile yommbila (I-Bassareo kunye ne-Di Chiara, i-1997, Hajnal et al., 2004, U-Liang et al., 2006, Phawula et al., 1991, URada et al., 2005b). Ukunyuka kwe-extracellular DA kungasigqiba isidlo kwiigundane eziswele ukutya (UHernandez kunye noHoebel, 1988). Nangona kunjalo, kwizilwanyana ezityebileyo, oku kukhutshwa kwe-DA kubonakala ngathi kuxhomekeke kubunewunewu kuba inqwenela ukufikelela okuphindaphindiweyo, nokuba ukutya kumnandiI-Bassareo kunye ne-Di Chiara, i-1997, URada et al., 2005b). Isimo esisichazayo, esichazwe ngezantsi (Icandelo 5.C.), Xa izilwanyana zihlutha ukutya kwaye zitye iswekile rhoqo.

I-extracellular DA iyancipha ekuphenduleni ukurhoxiswa kweziyobisi (I-Acquas et al., 1991, I-Acquas ne-Di Chiara, i-1992, URada et al., 2004, URossetti et al., 1992). Iimpawu zokurhoxa kumachiza e-dopaminergic zichazwe kakuhle kunalezo ziqwalaselwayo ngexesha lokurhoxiswa kwee-opiates. Ke ngoko, kunokuba lula ukuqonda iimpawu zokurhoxisa xa usebenzisa ukutya okukhulula zombini i-DA kunye nee-opioids. Iswekile yenye yokutya okunje.

3.B. Iipioids

Iipptide ze-opioid zibonakaliswa kakhulu kuyo yonke inkqubo ye-limbic kwaye zinxulunyaniswa neenkqubo ze-DA kwiindawo ezininzi ze-forebrain (Haber kunye noLu, 1995, I-Levine kunye neBillington, 2004, I-Miller kunye nePickel, 1980). Iinkqubo ze-opioid ze-opioid zikhupha ezinye zeziphumo zazo zokuqiniswa kokusebenza ngokusebenzisana neenkqubo ze-DA (U-Bozarth kunye noWise, 1986, I-Di Chiara kunye ne-Imperato, i-1986, I-Leibowitz kunye neHoebel, i-2004). I-opioid peptide enkephalin kwi-NAc inxulumene nomvuzo (Iibhali-Kubik et al., 1989, U-Bozarth kunye noWise, 1981, Endala, 1982, I-Spanagel et al., 1990) kwaye inokuthi isebenze zombini i-mu kunye ne-delta receptors ukwandisa ukukhutshwa kwe-DA (I-Spanagel et al., 1990). Ukuguqulwa kwesifo se-Morphine kuguqula imbonakalo ye-pioides ze-opioid ngelixa inyusa imveliso ye-peptide ye-opioid kwi-NAc (Przewlocka et al., 1996, I-Spangler et al., 2003,I-Turchan et al., 1997). Ii-opioids zikwabalulekile kule nkqubo njengama-cotransmitter ane-GABA kwezinye i-accumbens kunye nemiphumela yokukhuphela kwe-drial striatal (Kelley et al., 2005).

Ukusetyenziswa okuphindaphindiweyo kwee-opiates, okanye ezinye iziyobisi ezingezizo ii-opiate, kungakhokelela kwimvakalelo ye-mu-opioid receptor kwimimandla eliqela, kubandakanya i-NAc (Koob et al., 1992, I-Unterwald, 2001). Umchasi we-mu-receptor ochasene ne-NAc uya kujonga iziphumo ezivuzayo ze-heroin (UVaccarino et al., 1985), kwaye ngokweenkqubo ezinjalo iziyobisi zisetyenzisiwe njengonyango kunyango lotywala kunye nokuxhomekeka kwe-heroin (Deas et al., 2005, Ukunyanzelwa et al., 2003, UMartin, 1975, I-O'Brien, 2005, I-Volpicelli et al., 1992).

Ukufakwa kokutya okunokutya kunesiphumo se-opioids endo native kwiindawo ezahlukeneyo zesayithi (Dum et al., 1983, I-Mercer kunye ne-Holder, i-1997, I-Tanda kunye ne-Di Chiara, i-1998), kunye inaliti ye-mu-opioid agonists kwi-NAc yonyusa ukutya ukutya okunencasa enamafutha okanye iswekile (Zhang et al., 1998, UZhang noKelley, 2002). Abachasene ne-opioid, kwelinye icala, ukuncipha kokutya okumnandi kunye nokunciphisa ukutya ukutya okunencasa, ukutya okukhethwayo, nkqu nakwidosi ezinganampembelelo kukutya okumgangatho ofanelekileyo (Iglasi et al., 1999). Olu nxibelelaniso lwe-opioid-palatability lubonakaliswa ngakumbi ziithiyori apho isisongelo sokuqina sidityaniswa kwinkqubo ye-dopaminergic yenkuthazo yenkuthazo kunye ne-opioid "ukuthanda" okanye "ulonwabo" lweempendulo ze-hedonic (EBerridge, 1996, URobinson noBerridge, i-1993, I-Stein, 1978). Ubungqina bokuba ii-opioids kwi-NAc zinefuthe lokuphendula kwe-hedonic zivela kwidatha ebonisa ukuba i-morphine iphucula i-rats 'incasa yobumnandi bokujongana kwakhona kwesisombululo kwisisombululo esimnandi emlonyeni (IPecina kunye neBerridge, 1995). Ukungafani phakathi kweenkqubo “zokufuna” kunye “nokuthanda” kukwacetyiswa zizifundo ebantwini (I-Finlayson et al., 2007).

3.C. I-acetylcholine

Iinkqubo ezahlukeneyo ze-cholinergic kwingqondo ziye zachaphazeleka kukutya kunye nokutya iziyobisi, kwaye zinxulumene ne-DA kunye nee-opioids (Kelley et al., 2005, URada et al., 2000, AmaYuda, i-1995). Ukugxila kwii-interneurons ze-ACh kwi-NAc, ukulawulwa kwenkqubo ye-morphine kunciphisa ukuvela kwe-ACh (Smith et al., 1984), ukufumanisa okungqinisisiweyo kwi vivo Ukuhanjiswa kwegciwane kwimigudu yokuziphatha ngokukhululekileyo (UFiserova et al., 1999, URada et al., 1991a, 1996). I-interneurons yeCholinergic kwi-NAc inokunyula ngokunganyanzelekanga i-enkephalin gene expression kunye nokukhutshwa kwe-peptide (Kelley et al., 2005). Ngexesha lokurhoxiswa kwe-morphine, i-ACh eyongezelelweyo ye-ACh inyuka kwi-NAc ngelixa i-DA iphantsi, iphakamisa ukuba le meko ye-neurochemical ingabandakanyeka kumanqanaba okurhoxisa ukurhoxa (I-Pothos et al., 1991, URada et al., 1991b, 1996). Ngokunjalo, zombini i-nicotine kunye nokurhoxiswa kotywala kuyonyusa i-extracellular ACh, ngelixa kunciphisa iDA kwi-NAc (UDe Witte et al., 2003, URada et al., 2001, 2004). Le meko yokurhoxa inokubandakanya ukudakumba ngokuziphatha, ngenxa yokuba i-M1-receptor agonists ityunyiwe kwi-NAc inokubangela uxinzelelo kuvavanyo lokuqubha (U-Chau et al., 1999). Indima ye-ACh ekurhoxiseni iziyobisi iye yabonakaliswa ngakumbi ngendlela elawulwa ngendlela eyi-acetylcholinesterase inhibitors, enokuthi ibeke imiqondiso yokurhoxa kwizilwanyana ezingaxhomekekanga (Katz kunye noValentino, 1984, I-Turski et al., 1984).

I-ACh kwi-NAc ikwabethelelwa nakukutya. Sikholelwa ukuba isiphumo sayo esipheleleyo se-muscarinic kukuthintela ukondla kwii-receptors ze-M1 kuba inaliti yasekhaya ye-musonisis edonist arecholine iya kuthintela ukondliwa, kwaye isiphumo sinokuthi sithintelwe yi-pirenzapine ye-M1 echasene ne-pirenzapine (Rada neHoebel, engashicilelwanga). Ukondla ngokugcuma konyuka kwe-ACh yangaphandle kwi-NAc (Avena et al., 2006, Phawula et al., 1992). Ukucamngca ngomkhwa okunemeko ikwenyusa i-ACh kwi-NAc kwaye kwangaxeshanye iphantsi i-DA (Phawula et al., 1991, 1995). I-D-fenfluramine edityaniswe ne-phentermine (Fen-Phen) yonyusa i-ACh ye-ext kwi-NAc kwi-NAc kwithamo elithintela ukutya kunye nokuzilawula kwe-cocaine (Glowa et al., 1997, URada kunye noHoebel, 2000). Iigundane ezinezilonda ezibangelwa kukukhupha i-ACh izilonda ze-hyperphagic ziyalingana kwiigundane ezingasetyenziswanga (Hajnal et al., 2000).

I-DA / ACh ibhalansi ilawulwa ngokuyinxenye ziinkqubo ze-hypothalamic zokondla kunye nokuzonwabisa. I-Norepinephrine kunye ne-galanin, ekhuthaza ukutya xa kufakwe i-penventricular nucleus (PVN), i-Abens ephantsi ye-ACh (Hajnal et al., 1997, URada et al., 1998). Umahluko yi-neuropeptide-Y, ekhuthaza ukutya xa kufakwa kwi-PVN, kodwa ayonyusi ukuphuma kwe-DA okanye ukwehlisa i-ACh (URada et al., 1998). Ngokuhambelana ithiyori, indibaniselwano yokuvelisa satiety yeserotonin kunye ne-CCK inaliti kwi-PVN inyusa i-accumbens ACh (IHelm al al., 2003).

Kubangela umdla kakhulu ukuba xa i-DA iphantsi kwaye i-ACh iphantsi kwaye iphakamileyo, oku kubonakala kungadali satiety, kodwa endaweni yephiko eliphikisayo (Hoebel et al., 1999), njengaxa unexhala lokuziphatha (I-Zangen et al., 2001, URada et al., 2006), ukurhoxiswa kweziyobisi (URada et al., 1991b, 1996, 2001, 2004) kunye noguquko olunencasaPhawula et al., 1995). Sigqiba kwelokuba xa i-ACh isebenza njenge-agonist ye-post-synaptic ye-M1 ineziphumo ezichasene ne-DA, kwaye ke ingasebenza njenge "brake" kwimisebenzi yedopaminergic (Hoebel et al., 1999, URada et al., 2007) kubangela ukuqaqadeka xa iDA iphakamileyo kunye noxinzelelo lwendlela yokuziphatha xa iDA iphantsi kakhulu.

4.A. "UkuBambisa": Ukukhukuliswa kokutya iswekile yemihla ngemihla kunye nokutya okukhulu

Ukunyanzelwa kobuthathaka luphawu lweziyobisi zokuxhatshazwa. Oku kunokuba yindibaniselwano yonyamezelo, apho into eninzi exhonyiweyo ifunekayo ukuvelisa iziphumo ezifanayo ze-euphoric (UKoob noLe Moal, i-2005), kunye novakalelo, njengoluvo lwe-locomotor, apho into ivelisa khona ukusebenza okuphuculweyo kokuziphatha (UVezina et al., 1989). Izifundo ezisebenzisa ukuzilawula ngokwamachiza zihlala zikhawulela ukufikelela kwiiyure ezimbalwa ngemini, ngexesha apho izilwanyana ziya kuzilawula ngokwazo ngokunqamleza okwahluka njengesiqhelo sedosi efunyenweyo (UGerber kunye noWise, 1989) nangendlela egcina i-extracellular ye-DA iphakanyiswe ngaphezu kwesiseko, okanye "indawo yokuqalisa" kwi-NAc (Ranaldi et al., 1999, Wise et al., 1995). Ubude bofikelelo lwemihla ngemihla kubonisiwe ukuba kuchaphazele kakubi ukuzilawula kokuzilawula okulandelayo. Umzekelo, eyona cocaine iyenziwa ngokwakho ngexesha le-10 ye-min yeseshoni xa ukufikelela okungenani kwe-6 h ngemini (U-Ahmed noKoob, i-1998). Amaxesha anqamlekileyo okufikelela, ukwenza "ukubotshwa", ibe luncedo, kuba indlela yokuziphatha elawula ngokwayo iyafana naleyo yomsebenzisi olinyanzelekileyoUMarkou et al., 1993, UMutschler kunye noMiczek, 1998, O'Brien et al., 1998). Naxa iziyobisi, ezinjenge-cocaine, zinikwa ukufikelela okungenamkhawulo, abantu okanye izilwanyana zaselebhu ziya kuzihambisa ngokwazo iziqwengana eziphindaphindiweyo okanye "ukuntywila" (U-Bozarth kunye noWise, 1985, I-Deneau et al., 1969). Nangona kunjalo, ukufikelela okwa ngokuphakathi okungena kulingo kungcono kunokuba ad adum Ukufikelela kwiinjongo zesilingo, kuba kunokwenzeka ukuba isilwanyana sithathe okungenani ukungxinana okukhulu ekuqaleni kwexesha lokufumaneka kwesiyobisi. Ngapha koko, ixesha lokuthintelwa kokutya linokuphucula ukubakho kwesiyobisi (Carr, 2006, I-Carroll, i-1985) kwaye ubonisiwe ukuba avelise ubucukubhede obucekeceke kwinkqubo ye -accaccumbens ye-DA (I-Pan et al., 2006).

Iziphumo zokufumanisa okuneswekile ziyafana nezo zibonwa ngamachiza okuphatha gadalala. Amantshontsho atyiwa iswekile yemihla ngemihla kunye ne-chow ekhulisa ukutya okuneswekile kwaye andise ukutya ngexesha leyure yokuqala yokufikelela yemihla ngemihla, esiyichaza njenge "binge" (Colantuoni et al., 2001). Izilwanyana ezine ad adum ukufikelela kwisisombululo seswekile kuthanda ukusela kuyo yonke imini, kubandakanya ixesha labo lokungasebenzi. Omabini la maqela andisa ukuwahlutha kwawo onke, kodwa izilwanyana ezingafikelelekiyo zisebenzisa iswekile eninzi kwi-12 h njengoko ad adum-izilwanyana ezenziwa kwi-24 h. Uhlalutyo olucacileyo lwephethini yokutya usebenzisa imeko yokusebenza esebenzayo (umlinganiselo we1) ibonisa ukuba izilwanyana ezinqamlekileyo zisebenzisa isidlo esikhulu seswekile ekuqaleni kokufika, kwaye zikhulu, zimbalwa izidlo zeswekile ngalo lonke ixesha lokufikelela, ngokuthelekiswa nezilwanyana ezisela iswekile ad adum (Ikhiwane. 1; IAvena kunye neHoebel, ezingashicilelwanga). Iigundane ezondliwa mihla le I-Intermittent Iswekile kunye neChow zilawula ukungena kwazo kwe-caloric ngokunciphisa ukutya kwazo i-chow ukuze zibuyisele iikhalori ezongezelelweyo ezifunyenwe kwishukela, ezibangela ubunzima bomzimba obuqhelekileyo (Avena, Bocarsly, Rada, Kim no Hoebel, abangashicilelwanga, IAvena et al., 2003b, Colantuoni et al., 2002).

 

Umzobo 1

Uhlalutyo lwesidlo lweempuku ezimbini ezimele ezihlala kumagumbi asebenzayo. Le igcinwe kwi-Intermittent ye-Daily Intermittent uSunrose kunye neChow (imigca emnyama) yayinokutya okunyukayo kweswekile xa kuthelekiswa nomnye u-Ad libitum Sucrose kunye neChow (imigca engwevu). IYure 0 yi4 ...

4.B. “Ukurhoxa”: Ukuxhalaba kunye noxinzelelo lwendlela yokuziphatha ebangelwa yi-opioid-antagonist okanye ukunqongophala kokutya

Njengoko kuchaziwe kwiCandelo 2, izilwanyana zingabonisa iimpawu zokurhoxa kwe-opiate emva kokubhengeza okuphindaphindiweyo xa into yokuxhatshazwa isuswe, okanye i-receptor efanelekileyo ye-synaptic ivaliwe. Umzekelo, umchasi we-opioid unokusetyenziselwa ukwenza ukurhoxa kwimeko yokuxhomekeka kwe-opiate (Espejo et al., 1994, Koob et al., 1992). Kwiigundane, ukurhoxiswa kwe-opiate kubangela iimpawu ezinobunzima zesomali (UMartin et al., 1963, Indlela et al., 1969), ukwehla kubushushu bomzimba (Ary et al., 1976), ubundlongondlongo (U-Kantak kunye noMiczek, 1986), kunye noxinzelelo (Schulteis et al., 1998), kunye nesifo eshukumisayo esibonakaliswa yi-dysphoria kunye noxinzelelo (I-De Vries kunye ne-Shippenberg, i-2002, UKoob noLe Moal, i-1997).

Ezi zibonakaliso zokurhoxiswa kwe-opioid ziye zaqatshelwa emva kokungena kwishukela ngexesha lokurhoxiswa kwamayeza kunye ne-opioid antagonist, okanye xa ukutya kunye noshukela kususwe. Xa ulawulwa ngethamo eliphezulu le-opioid antagonist naloxone (3 mg / kg, sc), iimpawu ezithile zokurhoxa, ezinjengokuncokola kwamazinyo, ukuthuthumela kwangaphambili, kunye nokuhlunguzelwa yintloko kuyajongwa.Colantuoni et al., 2002). Ezi zilwanyana ziba nexhala, njengoko kulinganiswa ixesha elincitshisiweyo elichithwe kwingalo etyhidiweyo yecala lokudibanisa izilwanyana (Colantuoni et al., 2002) (Ikhiwane. 2).

 

Umzobo 2

Ixesha elichithwe ezingalweni ezivulekileyo ze-maze ephezulu. Amaqela amagundane amane agcinwa kwizidlo zawo kwinyanga enye aze afumana i-naloxone (3 mg / kg, sc). Iqela le-Intermittent Glucose kunye neqela leChow bachitha ixesha elincinci kwiingalo ezivulekileyo ...

Uxinzelelo lwezinto oziphetheyo luye lwafunyanwa ngexesha lokurhoxiswa kwe-naloxone ekwixesha elizayo kwiigundane ezineswekile. Kolu vavanyo, iigundane zanikwa uvavanyo lwe-5-min lokunyanzelwa-apho uvavanyo lokubaleka (ukubhukuda nokukhwela) kunye nokuziphatha okuthe tyaba (ngokuhamba). Emva koko iigundana zahlulwa zangamaqela ezine ezazondliwa nge-Intermittent ye-Daily Intermittent kunye neChow, i-Daily Intermittent Chow, i-Ad libitum Sucrose kunye neChow, okanye i-Ad libitum Chow yeentsuku ze-21. Ngomhla we-22, ngexesha apho iigundane ezondliwe okwexeshana ziya kufumana iswekile yazo kunye / okanye i-chow, zonke iigundane ziye zalanyathelwa nge-naloxone (3 mg / kg, sc) ukurhola ukurhoxa kwaye emva koko zabekwa emanzini kwakhona olunye uvavanyo. Kwiqela ebelondliwe i-Intermittent ye-Daily Intermittent ne-Chow, indlela yokuziphatha yokubaleka yacinezelwa kakhulu ngokuthelekiswa ne-Ad libitum Sucrose kunye neChow kunye ne-Ad libitum Chow control (Ikhiwane. 3; UKim, uAvena kunye noHoebel, ongashicilelwanga). Oku kuncipha kwemizamo yokubaleka ethathelwe indawo kukuntywila okunyibilikayo kubonisa ukuba iigundane zazinengxaki yokuziphatha ngexesha lokurhoxa.

 

Umzobo 3

Iigundane ezigcinwe kwi-Daily Intermittent Sucrose kunye neChow azinakushukuma kunamaqela olawulo kuvavanyo lokuqubha ngenkani ngexesha lokurhoxa okumiselweyo. * p <0.05 ngokuthelekiswa neAd libitum Iswekile kunye neChow kunye neAd libitum Chow amaqela. ...

Iimpawu zokurhoxiswa kwe-opiate nazo ziyavela xa konke ukutya kususwa nge-24 h. Kwakhona oku kubandakanya iimpawu ezizodwa ezinjengokuncokola kwamazinyo, ukungcangcazela kwangaphambili kunye nokuhlunguzeliswa yintloko (Colantuoni et al., 2002) kunye noxinzelelo njengoko lilinganiswa nge-plus-maze (Avena, Bocarsly, Rada, Kim and Hoebel, engashicilelwanga). Ukushenxisa okuzenzekelayo ekususeni iswekile kuxeliwe kusetyenziswa ukunciphisa ubushushu bomzimba njengesiqhelo (UWidman et al., 2005). Iimpawu zokuziphatha gwenxa zifunyenwe ngexesha lokuyekiswa kokutya okubandakanya ukufikelela kweswekile (I-Galic kunye nePersinger, 2002).

4.C. "Ukunqwenela": Ukuphendula ngokuphucula iswekile emva kokungavumi

Njengoko kuchaziwe kwiCandelo 2, "ukunqwenela" kwizilwanyana zaselebhu kunokuchazwa njengenkuthazo yokufumana into esetyenziswa gadalala (UKoob noLe Moal, i-2005). Emva kokuzihambisa ngokwamachiza okuxhatshazwa kwaye ke kunyanzeliswa ukuba bayeke, izilwanyana zihlala zisebenzela ekuphenduleni ngokungaphenduliyo (okt, ukuxhathisa ukuphendula), kunye nokunyusa ukuphendula kwabo kwi-cue zangaphambili ezinxulunyaniswa neyeza elikhula kunye nexesha (okt, ukufaka incubation) (I-Bienkowski et al., 2004, I-Grimm et al., 2001, Lu et al., 2004). Ukongeza, ukuba ichiza liya kuphinda lifumaneke, izilwanyana ziya kuthatha ngaphezulu kunokuba bezenzile ngaphambi kokuyeka (okt, "umphumela wokwethisa") (I-Sinclair kunye ne-Senter, i-1968). Oku kunyuka kwesisusa sokufumana into yokuxhatshazwa kunganegalelo ekubuyeleni kwakhona. Amandla "okunqwenela" abonakaliswa ziziphumo ezibonisa ukuba ngamanye amaxesha izilwanyana ziya kujamelana neziphumo ezibi zokufumana into yokuxhatshazwa njenge-cocaine okanye utywala (UDeroche-Gamonet et al., 2004, UDickinson et al., 2002, UVanderschuren no-Everitt, i-2004). Ezi zibonakaliso kwizilwanyana zaselebhu zilingisa ezo zibonwe ebantwini apho ukubonakaliswa kwenkuthazo eyayikudibene nechiza lokuphathwa gadalala kukhulisa iingxelo zakho zokunqwenela kunye nokubeka kwimeko yokubuyela kwimeko yesiqhelo (O'Brien et al., 1977, 1998).

Sisebenzise iparigigm yokusebenzisa “ukungancedi” ukuphanda ukuselwa kokusetyenziswa kweswekile emva kokuzinxwema kwiigundane ebezingxala iswekile. Ukulandela ukufikelela kwe-12-h imihla ngemihla kwishukela, i-rats lever Press ye-23% iswekile engaphezulu kuvavanyo emva kwe-2 wks yokutsala kunangaphambili.Ikhiwane. 4; Avena et al., 2005). Iqela eline-0.5-h ukufikelela kwansuku zonke kwi-sucrose akubonisanga siphumo. Oku kubonelela iqela lokulawula elihlanganayo apho iigundwane ziqhelene nokunambitha kwe-sucrose, kodwa azange ziyisebenzise ngendlela ekhokelela kwisiphumo sokuncitshiswa. Iziphumo zicebisa ukuba kutshintshwe ifuthe leswekile elisisigxina kwiiveki ezimbini zokusela, likhokelela ekunyuseni umthambo.

 

Umzobo 4

Emva kweentsuku ze-14 zokusela iswekile, iigundane ezazikade zinayo i-12-h ukufikelela kwansuku zonke kukonyusa uxinzelelo lwe-glucose ukuya kwi-123% yokuphendula ngaphambi kokuthintela, kubonisa ukunyusa iswekile. Iqela eline-0.5-h ukufikelela kwansuku zonke kwenziwe ...

Ukongeza, njengamachiza achazwe apha ngasentla, inkuthazo yokufumana iswekile ibonakala ngathi "incubate", okanye ukukhula, ngobude bokuziyeka (UShalev et al., 2001). Sebenzisa imeko yokusebenza Igrimm kunye noogxa (2005) fumana ukuba ukufuna kwe-sucrose (ukucinezela i-lever yokutshabalalisa kunye ne-cue-paired cue) yonyuka ngexesha lokuthintela kumagundane emva kokufikelela iswekile kwiintsuku ze-10. Ngokumangalisayo, ukuphendula i-cue kwakukhulu emva kweentsuku ze-30 zokusela ishukela xa kuthelekiswa neveki ye-1 okanye usuku lwe-1. Ezi ziphumo zibonisa ukuvela kancinci kancinci kweenguqu zexesha elide kubuchwephesha be-neural obuphantsi kwesizathu sokuzilawula kunye nokusela iswekile.

4.D. "Ukuvuselela iminqamlezo": Ukunyuka kwempendulo ye-locomotor kwii-psychostimulants ngexesha lokuthintela iswekile

Imvakalelo yokuphembelela yokusetyenziswa kweziyobisi inokudlala indima ekuphuculeni ukuzilawula kwezamachiza kwaye iyanyanzeliswa njengento enegalelo kwikhoboka leziyobisi.URobinson noBerridge, i-1993). Kwilingo eliqhelekileyo lokuzivavanya, isilwanyana sifumana ichiza mihla le malunga neveki, ke le nkqubo iyema. Nangona kunjalo, kwingqondo kukho izinto ezingapheliyo, okanye ezikhulayo, iinguqu ezibonakala kwiveki okanye nangaphezulu xa kuthathwa idosi ephantsi, umngeni weziphumo zeziyobisi kwihyperlocomotion (Kalivas et al., 1992). Ukongeza, ubuntununtunu bokuwela kwelinye ichiza ukuya kwelinye kubonakalisiwe ngamachiza amaninzi okuxhatshazwa, kubandakanya i-amphetamine sensitizing rats to cocaine or phencyclidine (IGreenberg kunye neSegal, 1985, I-Kalivas kunye ne-Weber, i-1988, Pierce kunye neKalivas, i-1995, Schenk et al., 1991), I-cocaine enqamleza ngotywala (I-Itzhak noMartin, i-1999), kunye ne-heroin ene-cannabis (I-Pontieri et al., 2001). Olunye uphononongo lufumene ezi ziphumo kwizinto ezingekho iziyobisi. Uvakalelo lokuziphatha kwendlela yokuziphatha phakathi kwe cocaine noxinzelelo lubonakalisiwe (I-Antelman kunye neCaggiula, 1977, ICovington neMiczek, 2001, Prasad et al., 1998). Ukonyuka kokutya.Bakshi noKelley, 1994) okanye indlela yokuziphathaUFiorino noPhillips, 1999, Nocjar kunye nePanksepp, i-2002) kuqatshelwe kwizilwanyana ezinembali yokunyanzelwa iziyobisi.

Thina nabanye sifumanise ukuba i-Intermittent sukari ethatha iminqamlezo kunye neziyobisi zokuxhatshazwa. Amagundane aqondwe ngenaliti ye-amphetamine yemihla ngemihla (3 mg / kg, ip) ziimpawu ezixineneyo kwiveki enye kamva ekuphenduleni i-10% sucrose (IAvena kunye neHoebel, 2003a). Kwelinye icala, iigundane ezondliwa mihla le I-Intermittent Sugar kunye neChow zibonisa imbonakalo yokunqamla umnqamlezo kwi-amphetamine. Ngokukodwa, izilwanyana ezinjalo zi-hyperactive ekuphenduleni isezantsi, umngeni wedosi ye-amphetamine (0.5 mg / kg, ip) engenampembelelo kwizilwanyana ze-naïve, nasemva kweentsuku ze-8 zokusela iswekile (Ikhiwane. 5; IAvena kunye neHoebel, 2003b). Amagundane agcinwe kule shedyuli yokondla kodwa i-saline ephathisiweyo yayingasebenzi, kwaye iigundane zazingamaqela olawulo (I-Intermittent Chow yansuku zonke, i-Ad libitum Sugar kunye neChow, i-Ad libitum Chow) inikwe idosi yomceli mngeni. Ukufikelela okungaphakathi kwangaphakathi kukwafikelela nakwimimandla enqumleza ngecocaine (IGosnell, 2005) kwaye incedise kuphuhliso lokuvuselela amandla e-aginist quinpirole ye-DA (UFoley et al., 2006). Ke ngoko, iziphumo ezinama-agonist amathathu e-DA ahlukeneyo asuka kwiilebhu ezintathu ezahlukeneyo axhasa ithiyori yokuba inkqubo ye-DA ibonakaliswa kukungena kweswekile ngokuthe gqolo, njengoko kungqinwa yimvakalelo yomnqamlezo. Oku kubalulekile kuba ukuphuculwa kwe-neurotransication ye-mesolimbic dopaminergic kudlala indima enkulu kwiziphumo zokuziphatha kunye novakalelo lommandla (URobinson noBerridge, i-1993), kwaye inokuba negalelo kumlutha kunye nasekonwabeni ngokusetyenziswa gwenxa kweziyobisi.

 

Umzobo 5

Umsebenzi we-locomotor kwikheyibhile eyakhiwe njengepesenti yokuqhekeka kwesiseko somthi ngosuku 0. Amagundane agcinwa kwiintsuku ze-21 kwiirejimeni zokutya ezichaziweyo. Iigundane ezigcinwe kwi-Intermittent ye-Daily Intermittent kunye neChow zazinehyper kwiintsuku ezisithoba kamva ekuphenduleni ...

4.E. “Isango lokungena”: Ukonyusa isiselo esinxilisayo xa usiya iswekile

Izifundo ezininzi zifumanise ukuba ukuvavanya isiyobisi kwichiza elinye kunokukhokelela kungekuphela kwento eyenzeka emzimbeni, kodwa nakwindlela eyandileyo yokufumana elinye ichiza okanye into (U-Ellgren et al., 2006, IHenningfield et al., 1990, Hubbell et al., 1993, Liguori et al., 1997, I-Nichols et al., 1991, I-piazza et al., 1989, I-Vezina, 2004, UVezina et al., 2002, I-Volpicelli et al., 1991). Sibhekisa kule nto kuthiwa "kukunyanzeliswa kwemvakalelo yokuqonda". Kwiincwadi zoncedo lwezonyango, xa elinye ichiza likhokelela ekuthatheni elinye, oko kwaziwa ngokuba "sisango lokwenza". Kuyaphawuleka ngokukodwa xa ichiza elisemthethweni (umz. Inicotine) lisebenza njengendlela yokungena kwesiyobisi esingekho mthethweni (umzekelo, icocaine) (U-Lai et al., 2000).

Amagundane agcinwa ekufikeleleni kwiswekile yexeshana kwaye ke anyanzelwa ukuba abuyeke, kamva abonise ukuphuculwa kwe-9% yotywalaAvena et al., 2004). Oku kucebisa ukuba ukufikelela okwethutyana kwiswekile kunokuba sisango lokusetyenziswa kotywala. Abanye babonise ukuba izilwanyana ezithanda ukunambitheka okumnandi ziya kuzilawula ngokwazo i-cocaine ngomgangatho ophezulu (UCarroll et al., 2006). Njengakwindlela yokubonakalisa ukuthambeka kokuchazwa kwendlela echazwe apha ngasentla, phantsi kwale ndlela yokuziphatha kunokutshintsha kwengqondo engqondweni, njengokutshintsha kwezinto kwi-DA kunye nemisebenzi ye-opioid.

5.A. Ukutshintsha iswekile yokufunxa ukutya D₁, D₂ kunye ne-mu-opioid receptor yokubopha kunye nokubonisa kwe-mRNA

Iziyobisi zokuxhatshazwa zinokutshintsha i-DA kunye ne-opioid receptors kwimimandla ye-mesolimbic yengqondo. Izifundo ze-Pharmacological ezikhethiweyo D₁, D₂ kunye noD₃ I-receptor antagonists kunye nezifundo ze-gene zokunkqonkqoza ziveze ukuba zontathu ii-receptor subtypes ziphendulela kwiziphumo zokuqinisa iziyobisi zokuxhatshazwa. Kukho ukumiselwa komgaqo-nkqubo D₁ receptors (I-Unterwald et al., 1994) kunye nokunyuka kwe-D₁ I-receptor binding (IAlburges et al., 1993, I-Unterwald et al., 2001) ukuphendula icocaine. Ngokuchaseneyo, D₂ I-receptor density isezantsi kwi-NAc yeenkawu ezinembali yokusetyenziswa kwecocaine (Moore et al., 1998). Iziyobisi zokuxhatshazwa zinokuvelisa utshintsho kwi-gene expression of DA receptors. I-Morphine kunye necocaine ziboniswe ukuba zinciphisa i-DIYS₂ receptor mRNA (I-Georges et al., 1999, I-Turchan et al., 1997), kunye nokunyuka kwe-D₃ receptor mRNA (I-Spangler et al., 2003). Oku kufunyanwa zizilwanyana zaselebhu kuxhasa izifundo zekliniki, eziveze ukuba D₂ Ii-receptors zilawulwa phantsi kwizidakamizwa ze-cocaine (Volkow et al., 1996a, 1996b, 2006).

Iinguqu ezifanayo ziye zaxelwa ngokuhamba kwexesha ushukela. I-Autoradiography ityhila ukwanda kwe-D₁ kwi-NAc kunye nokuhla kwe-D₂ I-receptor ibopha kwi-striatum (Ikhiwane. 6; Colantuoni et al., 2001). Oku kwakuhambelana neegundane ezitywe nge-chow, ke ayaziwa nokuba ad adum iswekile iyakubonisa lempembelelo. Abanye baxele ukwehla kwe-D₂ I-receptor ebopha kwi-NAc yeempuku kunye nokufikelela kokuthintelwa kwe-sucrose kunye ne-chow xa kuthelekiswa namagundane anikezwe umda we-chow kuphela (Bello et al., 2002). Iigundane ezineswekile yexeshana kunye nokufikelela kwi -op₂ i-receptor mRNA kwi-NAc xa kuthelekiswa ad adum ulawulo lwe-chow (I-Spangler et al., 2004). amanqanaba e-mRNA e-D₃ I-receptor mRNA kwi-NAc iyonyuswa kwi-NAc kunye ne-caudate-putamen.

 

Umzobo 6

I-Intermittent iswekile zokungena eziguqukayo i-receptor ye-DA ibophelela kwinqanaba le-striatum. D₁ I-receptor yokubopha (ipaneli ephezulu) inyuka kwi-NAc engundoqo kunye neqokobhe lezilwanyana ezivezwe kwi-Intermittent Glucose kunye neChow (imivalo emnyama) yeentsuku ze-30 xa kuthelekiswa nolawulo ...

Ngokumalunga ne-opioid receptors, ukubopha i-mu-receptor kuyonyuswa ekuphenduleni i-cocaine kunye ne-morphine (Bailey et al., 2005, I-Unterwald et al., 2001, UVigano et al., 2003). I-Mu-opioid receptor yokubopha ikwaphuculwa kakhulu emva kweeveki ezintathu kwisidlo seswekile esetyenziswayo, ngokuthelekiswa ad adum chow. Iziphumo zaye zaqatshelwa kwigobolondo ye-accumbens, cingate, hippocampus kunye ne-locus coeruleus (Colantuoni et al., 2001).

5.B. I-Intermittent iswekile yokuthatha intsholongwane enkthalin mRNA expression

I-Enkephalin mRNA kwi-striatum kwaye i-NAc iyancitshiswa ekuphenduleni ngenaliti ephindaphindiweyo ye-morphine (I-Georges et al., 1999, I-Turchan et al., 1997, Uhl et al., 1988). Olutshintsho ngaphakathi kweenkqubo ze-opioid ziyafana nezo zibonwe kwizifundo ezixhomekeke ebantwini ze-cocaine (UZubieta et al., 1996).

Amagundane ngokufikelela iswekile kwakhona kubonakalisa ukwehla okukhulu kwe-enkephalin mRNA, nangona kunzima ukwahlulela ukubaluleka kwayo (I-Spangler et al., 2004). Oku kuncipha kwe-enkephalin mRNA kuyahambelana kwiziphumo ezijongwe kwiigundane kunye nokufikelela okulinganiselweyo kwemihla ngemihla kwisidlo esimnandi seoli,Kelley et al., 2003). Ukuthatha oku kuncipha kweziphumo ze-mRNA kwi-peptide encinci ye-encephalin eyenzelwe kwaye ikhutshiwe, inokuphendula ngokunyusa okunyanzelisiweyo kwi-receptors ze-mu-opioid, njengoko kukhankanyiwe apha ngasentla.

5.C. Ukutya iswekile yemihla ngemihla rhoqo kukhupha i-dopamine kwii-accumbens

Enye yezona zinto zixhaphakileyo phakathi kwemithambo yeswekile yokufumana iswekile kunye neziyobisi zokuxhatshazwa zifunyenwe zisetyenziswa kwi vivo Ukuvavanya i-Microsodial yokulinganisa i-extracellular DA. Ukunyuka okuphindaphindiweyo kwe-extracellular DA luphawu olubonisa iziyobisi ezisetyenziswayo. I-extracellular DA inyuka kwi-NAc ekuphenduleni zombini iziyobisi ezichasayo (I-De Vries kunye ne-Shippenberg, i-2002, I-Di Chiara kunye ne-Imperato, i-1988, I-everitt kunye neWolf, 2002, UHernandez kunye noHoebel, 1988, Ukukhalaza et al., 1988, IPicciotto kunye neCorigigall, 2002, I-Pothos et al., 1991, URada et al., 1991a) kunye neziphumo ezinxulumene neziyobisi (Ito et al., 2000). Ngokungafaniyo neziyobisi zokuphathwa gadalala, ezivelisa iziphumo zazo ekukhululweni kwe-DA ixesha ngalinye xa zilawulwa (I-Pothos et al., 1991, Wise et al., 1995), isiphumo sokutya ukutya okunencasa ekhutshwa kukukhutshwa kwe-DA kuya kuthambeka ngokufikelela okuphindaphindiweyo xa ukutya kungasasebenziyo, ngaphandle kokuba isilwanyana sinokutyaI-Bassareo kunye ne-Di Chiara, i-1999, UDi Chiara kunye noThanda, 1997, URada et al., 2005b). Ke ngoko ke, ukondla ngokwesiqhelo kwahluke kakhulu kunokuthatha iziyobisi kuba impendulo ye-DA ngexesha lokutya iphelisiwe.

Nangona kunjalo, kwaye oku kubaluleke kakhulu, iigundane zitya iswekile yexeshana rhoqo kwaye i-chow ngokuqinisekileyo ikhupha i-DA yonke imihla njengoko ilinganiswa ngeentsuku ze-1, 2 kunye ne-21 yokufikelela (Ikhiwane. 7; URada et al., 2005b). Njengolawulo, iigundane zitya iswekile okanye i-chow intengiso iigundane ezinokufikelela ngokuthe ngcembe kwi-chow, okanye iigundane ezinambitha iswekile izihlandlo ezibini kuphela, ziphuhlisa impendulo engaphendulwanga ye-DA njengoko kuyinto eqhelekileyo ukutya okutyayo. Ezi ziphumo zixhaswa ziziphumo zenguqu kwi-ascobs ye-DA kunye nothumelo lwe-DA kumagundane agcinwe kwishedyuli yokondliwa kweswekile (Bello et al., 2003, I-Hajnal kunye neNorgren, 2002). Ngokudibeneyo, ezi ziphumo zibonisa ukuba ukufikelela ngokuthe ngcembe kwiswekile nakwi-chow kubangela ukunyuka okuphindaphindiweyo kwi-DA yangaphandle ngendlela efana nesiyobisi sokuxhaphaza kunokutya.

 

Umzobo 7

Amagundane ngokufikelela okwethutyana kokukhutshelwa kweswekile kwi-DA xa uphendula ngokusela i-sucrose ye-60 min ngemini ye-21. Dopamine, njengoko ulinganiswe ngu kwi vivo i-Microdialysis, ulonyuso lwe-Intermittent Sucrose kunye neegow (ukujikeleza okuvulekileyo) ngeentsuku 1, 2 kunye ne21; okuchasene, ...

Umbuzo onomdla ngowokuba ingaba iimpembelelo ze-neurochemical ezibonwe ngokufikeleleka kweswekile ngenxa yezinto zayo zokugcina okanye ngaba incasa yeswekile inokwanela. Ukuphanda ifuthe leswekile, sisebenzise ulungiselelo lokutya lwe-sham. Iigundane ezinomdla sham nge-fistula ye-gastric evulekileyo inokukungenisa ukutya kodwa zingakugayi ngokupheleleyo (USmith, 1998). Ukutyisa nge-Sham akukuphelisi ngokupheleleyo iziphumo zokungena ngaphakathi (UBerthoud noJeanrenaud, 1982, Sclafani naseNissenbaum, 1985), nangona kunjalo ivumela izilwanyana ukuba zingcamle iswekile ngelixa zigcinwa phantse kungekho calories.

Iziphumo zokwenza iswekile yokondla iswekile kwiyure yokuqala yokufikelela mihla le zibonisa ukuba i-DA ikhutshwa kwi-NAc, nokuba ziiveki ezintathu zokuzinkcinkca mihla le, ngenxa yencasa ye-sucrose (Avena et al., 2006). Ukuzondla nge-sham akukuthuthuzi ngakumbi ukukhutshwa okuqhelekileyo kweswekile kwi-DA. Oku kuxhasa omnye umsebenzi obonisa ukuba isixa sokukhutshwa kweDA kwi-NAc kuhambelana noxinzelelo lwe-sucrose, hayi umthamo osetyenzisiweyo (Hajnal et al., 2004).

5.D. Ukukhutshwa kwe-acetylcholine ye-acumls kulibaziseka ngexesha lokuxutshwa kweswekile kwaye ipheliswe ngexesha lokutya kesham

Ukondla Sham kubonise iziphumo ezinomdla nge-ACh. Njengoko kuchaziwe kwiCandelo 3.C., Iqokelela i-ACh phakathi kwesidlo xa isondla ithoba kwaye emva koko ime (Phawula et al., 1992). Omnye unokuqikelela ukuba xa isilwanyana sithatha ukutya okuphezulu kakhulu, njengakuqala kwesisombululo seswekile kunye ne-chow, ukukhutshwa kwe-ACh kufanele kulibaziseke de kuqale inkqubo yokutya njengoko kubonakaliswe ekuphelisweni kancinci kwesidlo. Nantsi into eyayiqwalaselwayo; Ukukhutshwa kwe-ACh kwenzeka xa esi sidlo sokuqala "sokutya" sisondelaURada et al., 2005b).

Okulandelayo silinganise ukukhutshwa kwe-ACh xa isilwanyana singathatha isidlo esikhulu seswekile ngelixa sisitya isidlo sentsini. Ukuthenga iziqulatho zesisu kunciphise kakhulu ukukhutshwa kwe-ACh (Avena et al., 2006). Oku kungaqikelelwa kususelwa kwinkcazo yokuba i-ACh ihlala ibalulekile kwinkqubo yokufumana ulwalamano (Hoebel et al., 1999, Phawula et al., 1992). Ikwacebisa ukuba ngokucoca, umntu uphelisa impendulo ye-ACh echasa iDA. Ke xa "ukuluma" iswekile kuhamba kunye nokucoca, indlela yokuziphatha iqiniswa yi-DA ngaphandle kwe-ACh, enje ngokuthatha iyeza kwaye njengokuthanda ukutya okuqhelekileyo.

5.E. Ukurhoxiswa kweswekile kuphakamisa i-dopamine / ibhalansi ye-acetylcholine kwi-accumbens

Iimpawu zokuziphatha zokurhoxiswa kweziyobisi zihlala zihamba kunye notshintsho kubhaliso lwe-DA / ACh kwi-NAc. Ngexesha lokurhoxiswa, i-DA iyancipha ngelixa i-ACh inyuka. Oku kungalingani kubonisiwe ngexesha lokurhoxa ngokwemichiza- kunye neziyobisi ezininzi zokuxhatshazwa, kubandakanya morphine, i-nicotine kunye notywala (URada et al., 1996, 2001, 2004). Ukuyekiswa kwizinto ezinokusetyenziswa gwenxa kukwanele ukuveza iimpawu zokurhoxa. Umzekelo, amagundane anyanzelwa ukuba ayeke i-morphine okanye utywala anciphise i-DA yangaphandle kwi-NAc (I-Acquas ne-Di Chiara, i-1992, URossetti et al., 1992) kunye ne-ACh yonyuka ngexesha lokurhoxiswa okuzenzekelayo kwe-morphine (UFiserova et al., 1999). Ngelixa ukurhoxa kwichiza le-anxyolitic (diazepam) elenzelwe yi-bendodiazepine-receptor antagonist ayizithobi i-extracellular DA, iyakhupha i-Abencs ye-ACh, enokuba negalelo kukuxhomekeka kwe-benzodiazepine (URada kunye noHoebel, 2005)

Amagundane anokufikelela ngokuphakathi kwishukela kunye ne-chow ebonisa ukungalingani kwe-morocine ye-neurochemical kwi-DA / ACh ngexesha lokurhoxa. Oku kwaveliswa ngeendlela ezimbini. Njengoko kubonisiwe kwi Ikhiwane. 8, xa benikwa i-naloxone yokukhupha ukurhoxiswa kwe-opioid, kukho ukuncipha kokukhululwa kwe-DA kudityaniswa nokunyuka kokukhutshwa kwe-ACh (Colantuoni et al., 2002). Into efanayo yenzeka emva kwe-36 h yokupheliswa kokutya (iAvena, iBocarsly, iRada, uKim, iHoebel, engashicilelwanga). Enye indlela yokuguqula ukurhoxiswa-okubangelwa kukuphelisa kukucebisa ukuba ngaphandle kokutya ukukhupha ii-opioids, isilwanyana sithwala ubunzima obufanayo bokurhoxa ukubonwa xa ii-receptors ze-mu-opioid ezilawulwa zivinjelwe nge-naloxone.

 

Umzobo 8

I-extracellular DA (igrafu ephezulu) yehle iye kwi-81% yesiseko emva kwe-naloxone injin (3 mg / kg, sc) kwimigundane enembali ye-Daily Intermittent Sucrose neChow. I-Acetylcholine (igrafu esezantsi) inyuke iye kwi-157% kwimigangatho efanayo yokufikelela iswekile. ...

6.A. Bulimia amanosa

Uhlobo lokutya lwe-Daily Intermittent Iswekile kunye neChow kwabelana ngemikhwa ethile yendlela yokuziphatha yabantu abafunyaniswa benengxaki yokutya kakhulu okanye ukuba ne-bulimia. I-bulimics ihlala ikunqanda ukuthambisa ekuseni kakhulu emva kwexesha kwaye iphinde ibambe ngokuhlwa, ngokutya ukutya okuthandekayo (I-Drewnowski et al., 1992, UGendall et al., 1997). Aba baguli kamva bacoca ukutya, nokuba kukugabha okanye ukusebenzisa isisu, okanye kwezinye iimeko ngokuzilolonga (Umbutho we-Psychiatric Association, i-2000). Izigulana ze-Bulimic zinamanqanaba asezantsi β-endorphin (UBrewerton et al., 1992, Ububanzi et al., 1986), enokukhuthaza ukutya ngokuthanda okanye ngokunqwenela iilekese. Kananjalo banciphise i-receptor ye-mu-opioid ekubetheleleni insula ngokuthelekiswa nolawulo, olunxulumene nokuziphatha okutsha nje (UBencherif et al., 2005). Oku kwahluke kunye nokunyuka okubonwe kwiigundane kulandela ukulunywa. Ukujikeleza ngokujikelezayo kunye nokupheliswa kokutya kunokuvelisa utshintsho kwi-mu-opioid receptors, enceda ukuqhubekeka kokuziphatha okungxamisekileyo.

Sisebenzise ukutya kesham ukulinganisa ukuhlanjululwa okunxulumene ne-bulimia. Iziphumo ezifunyenwe zichazwe kwiCandelo 5.C., Ukuba ukufikelela rhoqo kweswekile kukhupha i-DA ngokuphendula incasa yeswekile, kunokuba kubalulekile ukuqonda indlela yokuziphatha ethoba umxhelo. I-DA iye yanyanzelwa kwi-bulimia ngokuyithelekisa ne-hypothalamic self-stimulation, ekhupha i-DA ngaphandle kweekhalori (Hoebel et al., 1992). Izigulana ze-Bulimic zinomsebenzi ophantsi we-DA njengoko kubonakaliswa kuhlalutyo lwe-metabolites ze-DA kulwelo lwespinal, elibonisa nendima ye-DA kwiimpendulo zabo ezingaqhelekanga kukutya (UJimerson et al., 1992).

Izinto ezifanayo ezihambelana nokuziphatha kunye nokuqhelana nengqondo ngokuchaphazela iswekile kunye nokutya iziyobisi ezichazwe apha ngasentla zixhasa ithiyori yokuba ukutyeba kakhulu kunye nengxaki yokutya, njenge-bulimia kunye ne-anorexia, inokuba neempawu "zokulutha" kwabanye abantu (UDavis kunye neClidge, 1998, UGillman kunye noLichtigfeld, 1986, UMarrazzi kunye noLuby, 1986, I-Mercer kunye ne-Holder, i-1997, URiva et al., 2006). Ithiyori yokulutha ngokuzenzekelayo iphakamise ukuba ezinye iingxaki zokutya zinokuba sisiyobisi kwii-opioids ze-endo native (Heubner, 1993, UMarrazzi kunye noLuby, 1986, 1990). Kwinkxaso, ukungasebenzi kakuhle kokutya ngendlela etyiwayo yokutya kunye nokuzifela yindlala kunokuvuselela imisebenzi ye-opioid endoid (I-Aravich et al., 1993).

Izigulana ze-Bulimic ziya kuluma kakhulu ngenxa yeeswidi ezingaqhelekanga ze-caloric (Klein et al., 2006), ephakamisa ukuba bafumana izibonelelo zokukhuthaza i-orosensory stimulation. Sibonisile ukuba ukucoca kushiya i-DA ingenakuphikiswa yi-ACH enxulumana ne-ACh kwii-accumbens (Icandelo le-5.D.). Le meko ye-neurochemical inokuba luncedo ekutyeni okugqithisileyo kokutya. Ngaphaya koko, iziphumo ezifumanekayo ezingena kwiswekile zokutya okuneswekile zinxibelelana ne-amphetamine kwaye zikhuthaza ukubusela (iZigaba 4.D. Kunye ne-4.E.) Zinokuba zinxulumene nokuzonwabisa phakathi kwe-bulimia kunye nokusetyenziswa gwenxa kweziyobisi (Ukubamba et al., 1994).

6.B. Ukutyeba kakhulu

Olu phando luxhaswe sisibonelelo se-USPHS i-MH-65024 (BGH), DA-10608 (BGH), DA-16458 (ubudlelwane ne-NMA) kunye neSiseko seNdlela.

Iphepha elichazayo ukuba awusenanto oyifunayo: Le fayili yeFayile yombhalo wesandla ongabhalwanga owamkelwe ukushicilelwa. Njengenkonzo kumakhasimende ethu sinika le ngcaciso yokuqala kwincwadi yesandla. Umbhalo wesandla uza kufumana ukukopishwa, ukufakela, nokuphonononga ubungqina obunokubakho ngaphambi kokuba kukhutshwe kwifomu yayo yokugqibela. Nceda uqaphele ukuba ngexesha lokuveliswa kweeprogram ezinokuthi zifumaneke ezinokuthi ziphazamise umxholo, kunye nazo zonke izisemthethweni ezichasayo ezisetyenziswa kwiphephancwadi.

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