Ikhemestioposchiism. Umbhalo obhaliweyo ifumaneka kwi-PMC Sep 8, 2009.
Ishicilelwe kwifomu yokugqibela ehleliweyo njenge:
Ikhemestioposchiism. Ngamana i-2009; I-42 (iSuppl 1): S32-S41.
Ishicilelwe kwi-Intanethi ngoMeyi 11, 2009. ikhonkco: I-10.1055 / s-0029-1216356
PMCID: PMC2739305
I-NIHMSID: I-NIHMS140629
UGeorge F. Koob, Ph.D.
Inguqulelo yokugqibela yomhleli yeli nqaku iyafumaneka apha Ikhemestioposchiism
Bona amanye amanqaku ku-PMC Wisdom nqaku epapashwe.
Abstract
Ukuthengiswa kweziyobisi kuchazwa njengento engapheliyo, ukubuyisela ukusetyenziswa kweziyobisi ngokunyanzelekileyo kweenkqubo zengqondo ze-hedonic. Ukusetyenziswa kweziyobisi okunyanzelekileyo kuhamba kunye nokusebenza okunciphisiweyo kwamacandelwana obuchopho ukuqiniswa kweziyobisi kunye nokuqeshwa kwamacandelwana obuchopho obugqwetha ukuqinisa okungalunganga kokurhoxa okushukumisayo. I-subctates ye-neural yokurhoxiswa okushukumisayo ("icala elimnyama" lokulutha) ibandakanya ukufunyanwa kwezinto ze-amygdala ezandisiweyo kunye neenkqubo zoxinzelelo lobuchopho, kubandakanya ne-corticotropin-ukukhulula into kunye norepinephrine. Olu tshintsho, xa ludityaniswa nomvuzo wempumelelo, luyanyanzeliswa ukuba luqhubekeke lukwimo yelizwe elinolwazelelelo olusisiseko esinamandla sokuphinda ubuye. Ukubuyela kwakhona kubandakanya indima ephambili kwi-amygdala ye-basolateral ekulameni iziphumo zesishukumiso sangaphambili esasinikezelwa ngaphambili ngokufuna iziyobisi kunye nokurhoxiswa kweziyobisi. I-amygdala ye-basolateral inendima ephambili ekuchaseni iinkumbulo zeemvakalelo ngokubanzi. I-hypothesis ekuthethwa ngayo apha kukuba iinkqubo zoxinzelelo lweengqondo ezivuselelwa ziziphumo ezisisiphumo sokurhoxiswa kwamachiza azinakwenza kuphela isiseko sokuqiniswa okugwenxa okuqhuba ngokufuna iziyobisi, kodwa kunye neendlela ezinokubakho zokuxhasa imeko yeemvakalelo kunye nokunceda ukuqhuba imeko yobukhoboka ngokubanzi.
Isakhelo seNgqondo
Iziyobisi, ezikwabizwa ngokuba kukuxhomekeka kwizinto, sisifo esibuhlungu esinganyangekiyo (i-1) inyanzeliso yokufuna kunye nokuthatha ichiza, (i-2) ukulahleka kolawulo ekunciphiseni umthamo, kunye (3) yokuvela kwesimo esingesihle seemvakalelo (umz. i-dysphoria, ixhala, ukungahambi kakuhle) xa ukufikelela kwesiyobisi kuthintelwe (kuchazwe apha njengokuxhomekeka). Nangona ukuvela kwesimo esingesihle ngokweemvakalelo asisiyo isimiselo esiqinisekileyo sokuxhomekeka kuxhomekeko kuchazwe ngu Unyango lweDigital diagnostic kunye neNcwadi yeNkcazo yeNgxaki yeNgqondo, 4th ushicilelo (DSM-IV, [4]), kukubonakaliswa kwento ebizwa ngokuba kukurhoxiswa kwenkuthazo. Kananjalo, sisikhombi esinye kwiDSM-IV kunye neempawu ezixhaphakileyo zokulutha [78]. Ngokonyango, ukusetyenziswa kwesiyobisi gwenxa kodwa okwethutyana ukwahluka kukusetyenziswa kweziyobisi okunyanzelekileyo kwaye kuvela ukubakho kwesiyobisi. Injongo ebalulekileyo yophando lwangoku lwe-neurobiological kukuqonda iindlela ze-neuropharmacological ne neuroadaptive ngaphakathi kwe-neurocircuits ethile eguqula ukuguquka ukusuka ngamanye amaxesha, ukusetyenziswa kweziyobisi ezilawulwayo kunye nokulahleka kokuziphatha kulawulo lokufuna iziyobisi kunye nokuthatha iziyobisi ezichaza ukulutha okungapheliyo. Ukusetyenziswa kweziyobisi gwenxa kuchazwe njengokuphazamiseka okuqhubeka ukusuka ekunyanzelisweni ukuya ekunyanzelweni komjikelo owonakeleyo ophakathi kwamanqanaba amathathu: ukuxakeka / ulindelo, ukunxila, kunye nokurhoxiswa / kuchaphazeleka impembelelo embi [41, 44, 45].
Iimbono ezahlukeneyo zethiyori, ukusukela kuvavanyo lwengqondo kunye nentlalontle kwinzululwazi yezesayensi, zinokuthathelwa phezulu ngala manqanaba mathathu, athiwethwe njengokondla omnye komnye, esiba nzulu ngakumbi, kwaye asuke ekuqiniseni nasekuqiniseni okungalunganga. Ukuqiniswa okuqinisekileyo kunokuchazwa njengemeko apho umboniso wonyuselo unyusa ubukho bempendulo, kwaye ukuqiniswa okungalunganga kunokuchazwa njengemeko apho ukususwa kovuselelo kukwandisa khona impendulo. I-subctates ye-Neural yokuqinisekisa ukuqiniswa kwepropathi yokuthatha iziyobisi kunye nokufuna iziyobisi kulawula icandelo le-neurobiology yokulutha. Nangona kunjalo, umsebenzi wakutshanje ugxile kwiinkqubo zokuqinisa ezingalunganga ezinxulunyaniswa nokususwa kwemeko yeemvakalelo engalunganga enxulunyaniswa nokuzikiswa kunye nokuyeka okungapheliyo kwinqanaba lokuchaphazeleka / inqanaba lokuchaphazeleka kunye nenqanaba lokucinga / lokulangazelela lomjikelo weziyobisi, ngokulandelelana [34, 37]. Inkqubo-sikhokelo eqingqiweyo isekwe kwimiba "yentshukumisa" yokulutha kunye nokugxininisa kutshintsho olusuka ekusetyenzisweni kweziyobisi ukuya kwisimo sengqondo apho kuvela imeko yeemvakalelo ezingezizo (umzekelo, idysphoria, ixhala, ukurhwaqeka; ukubiza "icala elimnyama") kuphuma xa ufikelelo iyeza lithintelwe kwaye libonelela ngesiseko esisisiseko sokuseka kweziyobisi kunye nentsingiselo yazo.
Imijikelezo emibini ye-neurobiological icetyiswa njengengxam kumanqaku e-hedonic yesizathu sokufuna iziyobisi: ukujikeleza kwe-neurobiological ekubandakanyekeni kokuqina kwezinto zokuqiniswa kwezidakamizwa zokuxhatshazwa (i-ventral striatal-pallidal-thalamic loops) kunye nokujikeleza kwe-neurobiological enxulumene nokufunyanwa kwabantu Iimpawu zokuqinisa ezingezizo zokunyanga iziyobisi zoxhatshazo (i-amygdala eyandisiweyo) (Umzobo 1). Uhlalutyo lwangoku luza kuphonononga iindlela ze-neurobiological zeziyobisi ezichaphazelekayo kumanqanaba ohlukeneyo kumjikelo weziyobisi, kugxilwe kwi-plastiki ye-neurocircuits enxulumene notshintsho ukusuka ekusetyenzisweni kwesiyobisi ukuya kuhlobo lweziyobisi, iziphumo ezixhasayo zokurhoxa kunye nokuyeka ukubhengeza, kunye Ukufana kunye nenkumbulo yeemvakalelo enceda ukugcina inkqubo yokulutha.
I-Neococuituitry yoNyanzeliso oluGqibeleleyo oluDakileyo kunye neziyobisi zoSetyenziso gwenxa
Inkqubo yomvuzo wobuchopho kudala icetyiswa ukusukela oko kwafunyanwa umvuzo wombane wokukhuthaza ubuchopho okanye ukuzikhuthaza okwenzekelayo [64] kunye nokufumanisa ukuba izilwanyana ziya kuzisebenzisa ngokwazo iziyobisi ngaphandle kwembali yokuxhomekeka [81]. Umvuzo wokukhuthaza ubuchopho ubandakanya ukubanzi kwe-neurocircuitry kwingqondo, kodwa ezona ndawo zibuchwephesha ezichazwe ngumvuzo ophantsi kakhulu zibandakanya ukugcwala kwengqiniba yangaphambili ye-medial exhuma indawo yecandelo le-ventral yento ephambili kunye ne-basal forebrain [64]. Nangona ugxininiso olukhulu belugxile kwindima yenkqubo yokunyuka kwe-monoamine kwinqanaba le-medial forebrain, ezinye iinkqubo ze-nondopaminergic kwi-medial forebrain bundle ngokucacileyo zinendima ephambili [27]. Ukudibana kwamachiza okuphathwa gadalala ngenkqubo ye-hypothesised umvuzo wagxininiswa kukujonga ukuba zonke iziyobisi zokuphathwa gadalala, xa zilawulwa ngokuchanekileyo, zinciphisa imingcipheko yokukhuthaza ubuchopho [47].
Iziphumo zokuqinisa ezinobungozi zeziyobisi zokuxhatshazwa zihamba phakathi ngokusebenza kwe-dopamine, i-serotonin, ii-peptides ze-opioid, kunye neenkqubo ze-γ-aminobutyric acid (GABA), nokuba kungokwenziwayo ngokuthe ngqo kwi-basal forebrain (ngokukodwa i-nucleus accumbens kunye ne-main nucleus ye-amygdala ) okanye ngezenzo ezingathanga ngqo kwindawo yendawo enezixhobo zangaphakathi [32, 35, 42, 61]. Ubungqina obuninzi buxhasa i-hypothesis yokuba inkqubo ye-dolamine ye-mesolimbic yenziwe ngokumangalisayo ngamachiza e-psychostimulant ngexesha lokuzilawula. Nangona iinaliti kuzo zonke iziyobisi zokuxhatshazwa zonyusa amanqanaba e-dopamine e-extracellular kwi-nucleus accumbens ngokulinganisa kwi vivo isazisi [14], ubukhulu becala lonyuko lwenzeka kwii-nucleus ze-ethanol, i-nicotine, kunye nee-opioids ngexesha lokuzilawula [15, 97]. Ukongeza, i-opioid kunye ne-ethanol self-management ayichaphazeleka ngokukhetha ukutshabalalisa kwenkqubo ye-mesolimbic dopamine [16, 60, 66, 69]. Iinkqubo zeSerotonin, ngakumbi ezo zibandakanya i-serotonin 5-HT1B ukusebenza kwe-receptor kwi-nucleus accumbens, nako kuye kwachukumiseka kwiziphumo eziqinisa amandla zeziyobisi ze-psychostimulant. Ii-receptors ze-peptide ze-opioid kwi-ventral striatum, indawo yecandelo le -ralral, kunye ne-amygdala ziye zathatyathwa ukuba ziphendule iziphumo zokuqinisa ze-opioid kunye ne-ethanol self-management, ubukhulu becala isekelwe kwiziphumo zabachasene ne-opioid. Iintsholongwane ezichasene ne-opioid ezichasene ne-nucleus accumbens kunye ne-nucleus ye-amygdala esebenzayo kakhulu ekuvinjelweni kwe-opioid kunye ne-ethanol self-management [28, 92]. Iinkqubo ze-GABAergic zenziwa zangaphambi nangokwe-postynaptical kwi-amygdala kwi-ethanol kwiidosi ezinobutywala, kwaye abachasi be-GABA abachaphazeleke kwi-amygdala block ethanol self-management (uhlaziyo, bona [35, 61]).
Amacandelo e-neural subctates kunye neendlela ze-neuropharmacological zeziphumo ezibi zokususwa kweziyobisi kunokubandakanya ukuphazamiseka kweenkqubo ezifanayo ze-neurochemical kunye ne-neurocircuits efakwe kwiziphumo ezilungileyo zokuqiniswa kweziyobisi zokuxhatshazwa, ebizwa ngokuba yi-neuroadaptation yangaphakathi kwinkqubo. Zonke iziyobisi zokuxhaphaza zivelisa ukuphakama kwimbuyekezo yomvuzo wobuchopho ngexesha lokurhoxa okunamandla [43], nakwimodeli yezilwanyana yotshintsho ukuba likhoboka, ukunyuka kwembuyekezo yomvuzo wobuchopho (okt, umvuzo ocothisiweyo) yangaphambi okwethutyana kunye nokunxibelelana kakhulu nokunyuka kokutya iziyobisi ngokufikelela okude [1, 31] (Umzobo 2).
Ngexesha lokurhoxa okunjalo, imisebenzi eye yancipha yenkqubo ye-mesocorticolimbic dopamine yenzeka, kunye nokuncipha komsebenzi wokusebenza kwi-pioide ye-opioid, i-GABA, kunye neenkqubo ze-glutamate kwi-nucleus accumbens kunye ne-amygdala. Ukulawulwa okuphindaphindiweyo kwee-psychostimulants kuvelisa ukuqhuba kokuqala kwe-dopamine kunye ne-glutamate neurotransuction kwi-nucleus accumbens [91, 96]. Nangona kunjalo, ukulawulwa okungapheliyo kukhokelela ekunciphiseni kwi-dopaminergic kunye ne-glutamatergic neurotransuction kwi-nucleus accumbens ngexesha lokurhoxa okukhulu [29, 97], iimpendulo ezichaseneyo zeendlela zokudluliselwa kwe-opioid receptor kwi-nucleus accumbens ngexesha lokurhoxiswa kwe-opioid [84], utshintsho kwi-GABAergic neurotransmission ngexesha lokurhoxisa utywala [25, 71], kunye nolwahluko olwahlukileyo lwengingqi yomsebenzi we-nicotinic acetylcholine receptor ngexesha lokurhoxiswa kwe-nicotine.
Izifundo zokucinga zomntu iziyobisi ngexesha lokurhoxa okanye ukurhoxa obonakalayo zinike iziphumo ezihambelana nezifundo zezilwanyana. Dopamine D2 Ukuncipha kwama-receptors (i-hypothesised ibonisa ukusebenza kwe-hypodopaminergic), kunye ne-hypoactivity yenkqubo ye-orbitofadalal infralimbic cortex yenzeka [95]. Ukwehla komvuzo kwimisebenzi ye-neurotransmitter kwenziwe ukuba kufakelwe igalelo elikhulu kwisimo esibi sokunxulunyaniswa nokupheliswa kweziyobisi kwangethuba kwaye kunokubangela utshintsho olude lwebhayoloji olunegalelo kubuchwephesha bokungakhathali nobuthathaka bokubuyela kwakhona.
I-Neococuituitry ye-Negative Reinforcing enxulunyaniswa nokuSetyenziswa gwenxa kweziyobisi zokuSetyenziswa gwenxa
Icala elimnyama lokulutha [43] icingelwe ukuba ibandakanye ixesha elide, ukuqhubekeka kweplastikhi ekusebenzeni kweesetyhula ze-neural zokushukuma iinkqubo ezishukumisayo zokufumana iinkqubo zokwenza umsebenzi eziqhuba amazwe aphikisayo. Inqanaba lokurhoxisa / elingelichaphazeli elichazwe apha ngasentla liqulethe izinto eziphambili zokushukumisela, njengokuchaphazeleka okungapheliyo, iintlungu zokomoya, isiduko, idysphoria, i-alexithymia, kunye nelahleko yokunyuswa kwemivuzo yendalo, kwaye iphawuleka kwizilwanyana ngokwanda kwamanqanaba emvuzo ngexesha lokurhoxa kuyo yonke iziyobisi ezikhulu zokuxhatshazwa. Isimangalo yingqondo esekwe kwi-hypothesis yokuba iisistim zobuchopho zikwindawo yokuphelisa umvuzo [41, 45].
Umbutho we-neuroanatomical obizwa ngokuba yi-amygdala eyandisiweyo unokumela isiseko secandelo le-neuroanatomical kwimiphumela emibi ekusebenzeni komvuzo ochazwa njengento yokuhlawula. I-amygdala eyandisiweyo idityaniswa yindawo yokulala yebhedi ye-stria terminalis, i-nucleus ephakathi ye-amygdala, kunye nomda wokutshintsha kwindawo yokuhambisa i-medial subregion ye-nucleus accumbens (iqokobhe le-nucleus accumbens). Nganye yezi ndawo ineendlela ezithile zokuhamba kunye nokujikeleza kwezinto ezifanayo. Icandelo lokwahlula i-amygdala eyandisiweyo ifumana uninzi lwezinto ezihambelana nolwakhiwo lwe-limbic, njenge-basolateral amygdala kunye ne-hippocampus, kwaye ithumele ii-efferents kwinxalenye ye-medial ye-ventral pallidum kunye ne-lateral hypothalamus, ngaloo ndlela ichaza ngakumbi indawo ethile yobuchopho ehambelana ne-classical limbic classic ( ngokweemvakalelo) ulwakhiwo lwenkqubo ye-extrapyramidal motor [2].
Iinkqubo ze-neurochemical ngaphakathi kwe-amygdala eyandisiweyo ebonelela ngesiseko se-neurochemical yengubo yangaphandle ingabanzi kwaye ibonise inkqubo ye-buffered tata yokugcina i-hedonic homeostasis [41]. Nangona kunjalo, indawo ekugxilwe kuyo ye-neurochemical yenkqubo ye-anotward ye-neurotransmitter yi-corticotropin-releasing factor (CRF), i-norepinephrine, kunye ne-dynorphin. I-CRF, i-norepinephrine, kunye ne-dynorphin ziyabhalwa kwakhona ngexesha lokuchazwa kweziyobisi okungapheliyo, ukuvelisa i-anversive okanye uxinzelelo olufana ne-state ngexesha lokurhoxa [36, 45].
Iinkqubo ezahlukeneyo ze-neurochemical ezibandakanya ukumodareyitha koxinzelelo zinokuthi zibandakanyeke ngaphakathi kwimithambo yeenkqubo zoxinzelelo lweengqondo ukuzama ukoyisa ukubakho kwesiyobisi esingapheliyo kunye nokubuyisela umsebenzi oqhelekileyo ngaphandle kokubakho kwesiyobisi-okubizwa ngokuba yi-neuroadaptation ephakathi kwenkqubo. I-hypothalamic-pituitary-adrenal axis kunye nenkqubo yoxinzelelo lweengqondo, zombini eziphakathi zi-CRF, zixinekile kulawulo olungapheliyo lweziyobisi zokuxhatshazwa, impendulo eqhelekileyo ye-adrenocorticotropic ye-hormone kunye ne-corticosterone kunye ne-amygdala eyandisiweyo ngexesha lokurhoxa okunamandla kuwo onke amachiza amakhulu ukuhlukunyezwa [43, 48]. Ukurhoxa okunamandla kwiziyobisi zokuxhatshazwa kunokongeza ukukhutshwa kwe-norepinephrine kwi-nucleus yebhedi ye-stria terminalis kunye nokunciphisa amanqanaba okusebenza kwe-neuropeptide Y (NPY) kwi-amygdala [65, 77].
Umzekelo, ngotywala, i-CRF inokuba nendima ephambili ekulamleni i-neuroendocrine, ukuzimela, kunye nokuphendula kokuziphatha kuxinzelelo kunye noxinzelelo oluqhuba ukusela kakhulu ngexesha lokuxhomekeka [40]. Imimandla ye-amygdala eyandisiweyo (kubandakanya icandelo eliphambili le-amygdala) inezinto eziphezulu ze-CRF terminals, imizimba yeseli, kunye nezinto ezamkelayo kunye nenxalenye yenkqubo yoxinzelelo lwe- "extrahypothalamic" CRF [57]. Izifundo ezininzi zibonakalise ukubandakanyeka kwenkqubo ye-amygdala eyandisiweyo ye-CRF ekulamleni iimpendulo zokuziphatha ezinxulumene nokoyika kunye nexhala [40]. Ngexesha lokurhoxiswa kwe-ethanol, iinkqubo ze-CRF ze-extrahypothalamic ziba yi-hyperactive, kunye nokunyuka kwe-CRF engaphandle ngaphakathi kwe-nucleus ephakathi ye-amygdala kunye ne-bed nucleus ye-stria terminalis yeempuku ezixhomekeke [19, 58, 65, 99], kwaye oku kubhangiswa kweenkqubo ze-CRF zobuchopho kuthathwa njengezikhohlisi zozibini zokuziphatha ezinje kunye nokuphuculwa kokuzilawula okuhambelana nokugxothwa kwe-ethanol. Ukuxhasa le hypothesis, i-subtype nonselective CRF receptor antagonists α-helical CRF9-41 kunye d-Phe CRF12-41 (intracerebroventricular ulawulo) ukunciphisa zombini ukuthothiswa kwe-ethanol-ukukhuthaza inkxalabo efana nokuziphatha kunye nokuzilawula kwe-ethanol kwizilwanyana ezixhomekekileyo [5, 93]. I-CRF receptor antagonists ikwachaza indlela yokuziphatha efana noxinzelelo [68] kunye nokuzilawula kwe-ethanol kwiigundane ezixhomekeke kwi-ethanol [19]. Ulawulo lwenkqubo yeCRF1 Abachasi banezenzo ezifanayo kwizimpendulo ezinje ngexhala ezinxibelelene nokuchithwa okungapheliyo kunye nokuzilawula ngexesha le-ethanol36]. Ezi datha zibonisa indima ebalulekileyo yeCRF, ngokuyintloko kumbindi weamygdala, ekulamleni ulawulo oluzimeleyo olunxulumene nokuxhomekeka. Iziphumo ezifanayo ziye zaqwalaselwa kunye nolawulo lwe-intravenous self-management olunxulumene nokufikelela okwandisiweyo kwe-heroin [24], icocaine [85], kunye nicotine [21].
Ezi ziphumo azicebisi kuphela kutshintsho ekusebenzeni kwee-neurotransmitters ezinxulumene neziphumo eziqinisekileyo zokunyanga iziyobisi zokuxhatshazwa ngexesha lokuphuhliswa koxhomekeko, njengokuncipha kwe-dopamine, ii-peptides ze-opioid, i-serotonin, kunye nomsebenzi we-GABA, kodwa nokufumana inkqubo yeCRF (Umzobo 3). Ezongeziweyo phakathi kwenkqubo neuroadaptations eyanyaniswa nokushenxiswa okususayo kubandakanya ukwenziwa kwenkqubo ye-dynorphin / κ opioid, ukwenziwa kwenkqubo yoxinzelelo lweengqondo norepinephrine, kunye nokuphanziswa kwenkqubo yeengcaphephe zengqondo ze-NPY [43]. Ukongeza, ukusebenza kwenkqubo yoxinzelelo lobuchopho kunokuba negalelo kungekuko kwisimo esibi sokuziphatha esimalunga nokuyekiswa okunamandla, kodwa kunye nokuba semngciphekweni kwabaxinzelelo abaqwalaselweyo ngexesha lokuzikhupha ebantwini. Zizonke ezi zifundo ze-neurochemical (ukusuka kumlutha weziyobisi (i-neurobiology) kunye nezifundo ze-neuroanatomical (ukusuka ekuziphatheni kwe-neuroscience) zibonisa isinhanha esityebileyo sendibaniselwano lweemvakalelo ezinxulumene "icala elimnyama lokulutha," oluchazwa njengokuphuhlisa imeko yeemvakalelo eqhubayo. ukuqiniswa okungalunganga kotywala.
Isiyobisi kunye nokuTshintsha
Enye ingxoxo yokunyanzeliswa kokudityaniswa kwe-amygdala eyandisiweyo kunye neemvakalelo zeemvakalelo zivela kwidatha ebanzi evela kwiLe Doux kunye noogxa, ababonise ukuhlangana kwentetho yokuphendula imeko yoloyiko kumbindi we-amygdala [50]. Izifundo kwi-neurocircuitry yesimo soloyiko lubonisa ukuba ukuvuselela okuvela kwi-auditory cortex kunye nentlungu evela kwi-somatosensory cortex kuguqukela kwi-amygdala yamuva, ethi ke iprojekti ihambise kwi-nucleus ephakathi ye-amygdala ukukhupha iindlela ezahlukeneyo zokuzimela kunye nokuziphatha kwindlela yokuphendula yoloyiko [50]. Mhlawumbi into ebangela umdla ngakumbi yile hypothesis yokuba inwebu ephakathi yeamygdala yinto ephambili kwi-neurocircuitry ebandakanyekayo ekuqhubeni iintlungu zokomoya [67]. Umgaqo we-spino (trigemino) -ponto-amygdaloid wendlela ethi iprojekti isuka kwiphondo le-dorsal ukuya kwindawo ye-mesencephalic parabrachial ukuya kwi-nucleus esembindini ye-amygdala yenziwe i-hypothesised ukuba ibandakanyeke kwintlungu yeemvakalelo [7]. Ngaphantsi kwesi sikhokelo, iintlungu zibonisa ikhefu kunye neendlela zokulawula ubuchopho basekhaya ezibandakanya i-nociception.
Iimeko apho ii-opioids zithintela iintlungu kwaye zibuyisele i-homeostasis ziya kuba ziimeko zentlungu apho i-opioid ikhulula iintlungu kwaye ibuyisele isifundo kwimeko ye-heostic yekhaya; ke, iinkqubo ezichasayo azidingi kubandakanyeka. Nangona kunjalo, ukuba i-opioid eninzi ilawulwa, mhlawumbi ngenxa yokugqithisa ngokweqile okanye ukuguquguquka kwemithi, umzimba uya kusabela kuloo ntlekele ngokuzibandakanya kweenkqubo ezichasayo. I-Hyperalgesia ukuya kwii-opioids inokwenzeka kwizifundo ekuthi iopioid ngokwayo ivelise ikhefu nge-homeostasis. I-Hyperalgesia incinci kakhulu kunokwenzeka ukuba i-opioid ibuyisele i-homeostasis. Ukuzibandakanya okuphindaphindiweyo kweenkqubo ezichasayo ngaphandle kwexesha lenkqubo yokuvuselela i-homeostasis ayizukubandakanya i-hyperalgesia kuphela kodwa nenkqubo ye-allostatic echazwe ngezantsi. Ezo nkqubo zinokucelwa ngokunyanga ngedosi enkulu kakhulu ye-opioid, ukunyanga nge-opioid xa idosi isela ngaphezulu kwesidingo seentlungu ngenxa yemicimbi ye-pharmacokinetic, kunye / okanye ukunyanga umxholo ekungekho zintlungu kuwo (Koob GF, Shurman J, Gutstein H, iziphumo ezingapapashwa).
Ukurhoxiswa, ukuThintela okuKhuselweyo, kunye neAllostasis
Ukuphuhliswa kwemeko yeemvakalelo ezinxaxhileyo eqhubela phambili ukuqiniswa okungalunganga ichazwa njenge "icala elimnyama" lokulutha [43, 45] kwaye icetyisiwe ukuba ibe sisicatshulwa sokushenxisa esishukumisayo samandla e-hedonic eyaziwa njengenkqubo yokuchasa xa umphumo wokuqala wamachiza ungafezekanga. Imeko engentle yeemvakalelo equka inqanaba lokurhoxa / elingelichaphazeli elichazwe ngasentla linezinto ezishukumisayo eziphambili, njengokurhawuzelela okungapheliyo, iintlungu ngokweemvakalelo, malaise, idysphoria, alexithymia, kunye nelahleko yempembelelo yemivuzo yendalo ebantwini, kwaye ibonakaliswa kwiimodeli zezilwanyana ngokwanda koxinzelelo olufana nokuziphatha, iimpendulo ezinje nge-dysphoric, kunye nembuyekezo yemivuzo ngexesha lokurhoxiswa kwazo zonke iziyobisi eziphambili zokuxhatshazwa. Njengoko sele kukhankanyiwe apha ngasentla, iinkqubo ezimbini zenzelwa ukuba zenze isiseko se-neurobiological sokurhoxisa intshukumo: ilahleko yokusebenza kwiinkqubo zembuyekezo (ngaphakathi kwenkqubo neuroadaptation) kunye nokufunyanwa koxinzelelo lweengqondo okanye iinkqubo zangaphakathi (phakathi kwenkqubo neuroadaptation) [38, 41]. Njengokuxhomekeka kunye nophuhliso lokurhoxa, iinkqubo zoxinzelelo lobuchopho ezinje ngeCRF, norepinephrine, kunye ne-dynorphin ziyaqeshwa kwakhona, zivelise amazwe anxaxhileyo okanye oxinzelelo-olufana [45]. Kwangelo xesha, ngaphakathi kwimijikelezo yenkuthazo ye-amygdala ye-ventral eyandisiweyo, umsebenzi wokuvuza uyancipha. Umdibaniso wokuncipha kumvuzo we-neurotransmitter yomsebenzi kunye nokufumana iinkqubo zokwenza umsebenzi unike indawo enamandla okuqiniswa okungalunganga okunegalelo kunyanzeliso lokufuna iziyobisi kunye neziyobisi.
Umxholo wekhonkco uwonke uphakanyiswe apha kukuba umlutha weziyobisi umele ikhefu ngeendlela zokulawula ubuchopho basekhaya ezilawula imeko yeemvakalelo zesilwanyana. Nangona kunjalo, uluvo lokuba iziyobisi zimela ikhefu elilula kunye ne-homeostasis akwanelanga ukuchaza inani lezinto eziphambili zokulutha. Iziyobisi, ezifana nezinye iingxaki zempilo engapheliyo ezifana noxinzelelo lwegazi oluphezulu, ibaxeka ixesha elininzi, ziphantsi kwempembelelo ebalulekileyo yokusingqongileyo, kwaye ishiya umkhondo oshiyekileyo we-neuroadaptive ovumela "ukuphinda umlutha" kwinyanga kunye neminyaka emva kokudilizwa kunye nokuyeka. Ukubuyela umva, okanye ukubuyela ekusetyenzisweni gwenxa kweziyobisi kulandela amaxesha okusela, yenye yeempawu zomgaqo wokuxhomekeka kwinto yotywala. Ukuphuhliswa kokuxhomekeka kuphakanyisiwe ukuba kudlale indima ebalulekileyo kulondolozo lokusetyenziswa okunyanzelisiweyo kwaye uphinde ubuye emva kwexesha lokuyeka.
Kwiziselo ezinxilisayo zabantu, iimpawu ezininzi ezinokuthi zibonakaliswe ziimvakalelo ezimbi ziqhubeka ixesha elide emva kokurhoxa komzimba kwi-ethanol. Ezi mpawu, ukurhoqeka emva kwexesha elinobuzaza, zihlala zinomdla kwindalo kunye nokuzithoba kwaye zihlala ziphinda ziphinda ziphinde zenzeke. Imicimbi engendawo echasayo, kubandakanya iimvakalelo ezimbi njengezinto ezinomsindo, ukudandatheka, usizi, ixhala, kunye netyala, zizinto eziphambili ezikhokelela ekubuyeleni kwakhona [53]. Le meko ibizwa ngokuba "kukuziyeka" kwaye ichazwe ebantwini ababonisa i-Hamilton Depression rating ≥8 ngezi zinto zintathu zilandelayo eziphawulwe rhoqo zizifundo: uxinzelelo lokudakumba, unxunguphalo kunye netyala [53]. Umzekelo, ukukhathala kunye nokuxakeka kuxelwe ukuba kuyaqhubeka ukuya kwiiveki ze-5 emva kokurhoxiswa [3]. Ukuxhalaba kubonakalisiwe ukuphikelela ukuya kwiinyanga ze-9 [73], kunye noxinzelelo kunye nokudakumba kuboniswe ukuba banyamezele ukuya kwi-20-25% yotywala kude kufike kwi-2 iminyaka yokurhoxiswa.
Umsebenzi wezilwanyana ngokuxhomekeka kotywala ubonise ukuba ukuxhomekeka kwangaphambili kunokuhlisa "umqobo wokuxhomekeka" kangangokuba izilwanyana ebezixhomekeke ngaphambili zenziwe ukuxhomekeka ziphinde zibonise ukurhoxa okunzima komzimba kunye neempawu ezinje zokuxhalaba njengamaqela aqala ukufumana utywala okokuqala [6, 8]. Oku kuxhasa intelekelelo yokuba amava otywala kunye nophuhliso lokuxhomekeka ikakhulu kungakhokelela kwiinguqu ezisisigxina ekuphenduleni etywaleni. Nangona kunjalo, ukubuyela umva kuhlala kwenzeka nasemva kokuba iimpawu zokurhoxa okunamandla zivele, kucebisa ukuba utshintsho kwi-neuropharmacological olwenzeka ngexesha lokuphuhliswa koxhomekeko lunokuqhubeka ngaphaya kweempawu zokugqibela zokurhoxa ("protracted motivational leavingal syndrome"). Ukurhoxiswa okunjalo okunokubakho kusisiseko sentsingiselo. Imbali yokuxhomekeka kwiigundane kunye neempuku kunokuvelisa ukuphakama kwexesha elide kulawulo lwe-ethanol kwiiseshini zemihla ngemihla ze-30 ixesha elide emva kokurhoxiswa ngamandla kunye nokukhutshwa kwesidudu [70, 72]. Ukonyuka kokuzilawula kukodwa kuhamba kunye nokuphendula kokuziphatha okunyanzelekileyo kubaxinzelelo kunye nokunyusa ukuphendula kwabachasayo be-CRF receptor [46]. Olutshintsho oluqhubekayo kulawulo lwe-ethanol kunye nolwazelelelo lweentsalela koxinzelelo kunokuchazwa ngokungenakuzinziswa njengemeko “yokutsala.” Ukurhoxiswa kokurhoxiswa kumlinganiso ixesha emva kokurhoxa ngokomzimba kuye kwanyamalala xa ukuphakanyiswa kokutya okune-ethanol ngaphezulu kwesiseko kunye nokuziphatha okwandayo. ukuphendula uxinzelelo oluqhubekayo (i-2-8 iiveki emva kokurhoxiswa kwi-ethanol engapheliyo). Ukonyuka okuqhubekayo kokuzilawula iziyobisi ngexesha lokungakhathalelwanga kuye kwagxothwa ukuba kubandakanywe ukulungelelaniswa okufana nokwenzeka kwendawo yokuba umvuzo weziyobisi uphakanyisiwe (unyamezelo lwe-hedonic) [42]. Ezi mpawu zotywala iziyobisi zithetha ngaphezulu kokungasebenzi nje kwe-homeostatic ye-hedonic function kunye nolawulo oluphezulu, kodwa kunoko ikhefu elinamandla kunye ne-homeostasis yezi nkqubo zibizwa ngokuba yi-allostasis.
I-Allostasis, eyandulelayo yacaciswa ukuchaza ukungagugi kokuqhubeka komsebenzi nowokuzimela, ichazwa ngokuba "kukuzinza ngokutshintsha" [86]. I-Allostasis ibandakanya indlela yokuhambisa ngaphambili kuneendlela zokuphendula ezimbi ze-homeostasis, ngovavanyo oluqhubekayo lokuvavanywa kwesidingo kunye nohlengahlengiso oluqhubekayo lwazo zonke iiparameter ukuya kwiindawo ezintsha ezibekiweyo. Ke ngoko, eyona ndlela yokusebenza yokwenyama evumela iimpendulo ezikhawulezileyo kwimingeni yokusingqongileyo iba yenjini ye-pathology ukuba ixesha elaneleyo kunye nezixhobo azifumaneki ukuvala impendulo (umzekelo, unxibelelwano phakathi kweCRF, i-norepinephrine, kunye ne-dynorphin kwityala le-basal elingekhokelela kuxinzelelo lwendalo kunye nedysphoria) [33]. Zonke iindlela zenzelwa ukuba zibandakanyeke ekugcineni inkqubo yeemvakalelo yokusebenza kwengqondo ehambelana ne-pathology yokulutha [42]. Izinto ezimbini ezenzelwe ukuba ziphendule imeko yeemvakalelo ezingalunganga ezinxulunyaniswa nomlutha ziyancitshiswa izinto zokuhanjiswa kwembuyekezo yobuchopho kunye nokujikeleza kunye nokufumana ubuchwephesha bengqondo okanye iinkqubo zoxinzelelo (Umzobo 3). Imiceli mngeni ephindaphindiweyo, kunjalo kwimeko yeziyobisi zokuxhatshazwa, kukhokelela kwimizamo yengqondo ngokusebenzisa iimolekyuli, iselula, kunye notshintsho lwe-neurocircuitry ukugcina uzinzo kodwa ngeendleko. Iindleko ziyanda imeko yeemvakalelo ezimbi ngexesha lokurhoxa okunamandla kunye nokulingana nenkcazo yomthwalo we-allostatic [54]. Kwinkqubo yokusetyenziswa kweziyobisi echaziweyo apha, imeko yentsalela yeemvakalelo ithathwa njenge imeko yemibono yonke [42]. I-hypothesis enomdla ekufuneka icacisiwe apha ngezantsi kukuba iinkqubo ezifanayo zeemvakalelo ezibhekisele kwimpendulo "yokulwa okanye indiza" inokuthatha inxaxheba ekudibaniseni iinkumbulo ezinxulumene nomlutha.
Iziyobisi, isixhobo sokufunda, kunye nokukhumbula iimvakalelo
Ubungqina obuninzi bubonisa ukuba iziyobisi, kunye ngakumbi neziyobisi ze-psychostimulant, zinokuphucula ukusebenza kwengqondo. Iziphumo ezinjalo zinokubandakanya iintshukumo kumbono, ingqalelo, ukuvusa, kunye nokukhuthaza, kunye nokufunda kunye nememori. Nangona kunjalo, ngokubaluleke ngakumbi kwi-neurobiology yeziyobisi, iziyobisi zokuxhatshazwa zinokutshintsha imemori yeziphumo ezilungileyo kunye nezimbi zokuqiniswa kwezenzo zamachiza. Okubangela umdla ngakumbi kukuba ingaba inkumbulo yezenzo zamachiza inayo nayiphi na i-neural substrate egqithisa isiseko esithile esongezelelweyo kwiinkumbulo ezinjalo. I-hypothesis ekufuneka ithathelwe ingqalelo apha kukuba imigca emincinci yecala elimnyama lomlutha wobungqina obunamandla kunye ne-neural substrates yememori "yeemvakalelo".
Ubungqina obuninzi obuvela kwizifundo zabantu kunye nezilwanyana ziyayixhasa i-hypothesis yokuba iziyobisi zokuxhatshazwa zinokudlulisela imeko efanelekileyo yokuqiniswa kunye neepropathi zokuxhasa ezingalunganga. Iimpawu zezilwanyana zokunqwenela iziyobisi kunye nokubuyela umva ziyaqhubeka ukuphuhliswa kunye nokucocwa, kodwa ukuza kuthi ga ngoku zibonakalise imithombo yesibini yokuqiniswa njengokuqiniswa komgangatho [52, 87]. Isomelezi esimiselweyo sinokuchazwa njengaso nasiphi na isikhuthazi esingathathi hlangothi esifumana ukuqiniswa kwepropathi ngokudibana kunye nomqinisi ophambili. Kwimeko yokuqiniswa komgangatho obandakanya ukuzilawula iziyobisi, izifundo ziqeqeshelwa kwibhokisi esebenzayo enemigca emibini apho iimpendulo kwi-lever enye ziphumela ekunikezeleni ngesikhuthazo esifutshane esilandelwa sisitofu samachiza (i-lever esebenzayo), kunye neempendulo komnye umlobi Akukho ziphumo kulo lonke uvavanyo (i-lever engasebenziyo; [12, 82]). Emva koko, ukukwazi kokungathathi cala, amandla okuvuselela iziyobisi ukuze kulungiswe ukuphendula kwimeko yokungabikho kwamachiza amachiza kunika umlinganiso wexabiso lokuqiniswa lokukhuthaza. Ishedyuli yomyalelo wesibini yokuqinisa ingasetyenziswa njengomlinganiso weemeko zokuqina zokuphathwa kwamachiza [22]. Umsebenzi kwii-primates kunye neegunds kuphakamisa ukuba ukuphendula okuqinisekileyo kwe-cocaine kunokusekwa ngeshedyuli yoku-odola yesibini [79]. Ulawulo lweziyobisi olungazibandakanyiyo okanye isikhuthazo sangaphambili esinokuhanjiswa ngotywala ngokuhambisa iziyobisi sinokuphinda sifune ukuchitheka kweziyobisi kulandela ukutshitshiswa (ukubuyiselwa). Iziyobisi okanye iikati eziphediweyo ezinokuzilawula ngokwamachiza okanye ukuxela ukuzilawula ngokwamachiza kunokusebenza njengocalucalulo xa zisenziwa ngokungazithobiyo emva kokupheliswa kwaye ziya kubangela ukubuyiselwa kwemikhwa yokufuna iziyobisi [13, 82, 88]. Indawo yokuthanda indawo ekhethwayo yparadigm ikwabonelela ngomgangatho wokuqiniswa komgangatho, olingana ngokwamanqanaba anikezwe ngabasebenzi beparadigms. Uphononongo oluninzi olubanzi lubhalwe kwi-preference paradigm yendawo [10, 89, 90, 94].
I-subctates ye-neural yecandelo elinjalo lokuqinisa imeko yokuchaphazela iziyobisi zokuxhatshazwa, ngakumbi i-neural substrates yokubuyiselwa, kubandakanya ukubandakanyeka kweendlela ze-glutamatergic ukusuka kwi-cortex yangaphambili ukuya kwi-nucleus accumbens kunye nokusuka kwi-basolateral amygdala ukuya kwi-nucleus ephakathi ye-amygdala kunye ne-nucleus accumbens ( uphononongo, bona [17, 30, 83].
Ukurhoxiswa okunesimo esibambekayo kuye kwabonwa ekliniki. Owayesakuba likhoboka le-opioid wayehlala echaza iimpawu ezifana nokuyekiswa kwe-opioid xa ubuyela kwimeko ezinxulumene namava eziyobisi [62]. Kuphononongo lovavanyo lwangaphambili lweziyobisi ze-heroin ezigcinwe kwi-methadone, ii-opioid antagonist injections zaziphindaphindwe zenziwe ngesibini ithoni kunye nephuphu leppermint [63]. Inkcazo elandelayo yethoni kunye nevumba elivelileyo zombini iziphumo ezibi zokungonwabisi kunye neempawu ezibonakalayo zokurhoxa. Iziphumo ezifanayo ziye zaqatshelwa kuzo zombini iimodeli zamandulo kunye neentonga. Amaprimethi kunye neentonga ezivunyelwe ukuba zizenzele ii-opioids ngaphakathi kwe-23-24 h ngemini zacelwa umngeni kunye nomchasi we-opioid kunye nokukhuthaza okungathathi hlangothi ngaphambili. Umchasi we-opioid uchukumise ukunyuka okufana nokunyanzela ukuphendula i-opioid. Emva kokubhangqa okuphindiweyo, ukubonakaliswa kwenkuthazo eneemeko zodwa kuye kwabangela ukunyuka okubonakalayo kokuphendula i-opioid, ngokufana noko bekujongwe kunye nomchasi we-opioid yedwa [23, 31]. Iziphumo zokugxininisa ezingekho mgangathweni kweziyobisi zokuxhatshazwa zifundwe kuphela kwimeko yeziyobisi ze-opioid kwiimodeli zezilwanyana kodwa zibandakanya i-basolateral amygdala [80] kunye neendlela ezinokubakho ezinxulumene nemeko elungileyo yokomeleza iipropathi zeziyobisi zokuxhatshazwa. Nangona kunjalo, icandelo elibonakalisa ukurhoxa elinemeko ethile linokufumana kwakhona ukujikeleza kwengqondo okunyanzeliswa kukungabi namandla okunyanzelisa iipropathi zokurhoxiswa kweziyobisi kunye nokuyeka ukubhengeza. Ngokwenyani le "nkumbulo yeemvakalelo" inokuba negalelo kwimeko yobume beemvakalelo zokuqhubela phambili ukurhoxa.
I-subctates ye-neural yememori yeemvakalelo iphononongwe kakhulu kwaye idibene nezinye ii-neural substrates zokuqiniswa okuhle kunye nokubi okuhambelana neziyobisi zokuxhatshazwa. I-subctates ye-neural yenkumbulo yeemvakalelo ikwakha ukuhambelana okungathandekiyo kwe-neuropharmacological kunye ne-neural substrates ezinxulunyaniswa neemvakalelo ezingezizo ezinxulumene nokuthintela ukuxhomekeka kweziyobisi. Amava emvakalelo ahlala enxulunyaniswa neenkumbulo ezingapheliyo nezicacileyo eziye zachazwa njenge "inkumbulo zeflashbb "[11]. Indawo ephambili kwingqondo ephakathi ekuhlanganeni nokudityaniswa kweenkumbulo ezinjalo zeemvakalelo yi-amygdala ye-basolateral kunye nokudibanisa kweehormon zoxinzelelo kunye nezinye iinkqubo ze-neuromodulatory noradrenergic system eziqulathwe kuyo [55, 56]. Koluhlu lwezifundo ezibalaseleyo ezenziwe nguMcGaugh, Roosendal, kunye noogxa bakhe, i-amygdala yeasolgous yaboniswa ukuba iguqule imemori yokuguqula imiphumo yehomoni zoxinzelelo lwe-adrenal, nendima ephambili kusebenze lwe-noradrenergic Inkqubo ye-basolateral modulates yokudityaniswa kweentlobo ezininzi zolwazi. Kwizifundo zabantu, inqanaba lokuvula kwe-amgydala ngokweemvakalelo zokuvuselela ngokweemvakalelo kakhulu ngokukhumbula okulandelayo [9]. Ukongeza, njengoko kuphawuliwe apha ngasentla, i-amygdala ye-basolater inendima ephambili yokulamula imeko efanelekileyo kunye nemeko yokuqina engalunganga ehambelana neziyobisi zokuxhatshazwa.
Indima yeendlela ze-noradrenergic ekwandiseni ukudityaniswa kwememori yasungulwa kuthotho lwezifundo ezinenaliti yealadrenergic agonists kunye nabachasi kwi-amolgal basolateral. I-Norepinephrine okanye i-agonists ye-noradrenergic injeke ngqo kwi-amygdala ye-basolateral kwangoko emva koqeqesho iququzelela inkumbulo yemisebenzi yokuqeqesha evusa uvakalelo njengokuthintela ukuthintela [18], imeko yokwesaba imeko [49], umsebenzi wamhlaba wokumitha wamanzi [26], kunye nomsebenzi wokwamkelwa kwento [74]. Ukuhlatywa emva koqeqesho kwi-β-noradrenergic antagonists eneziphumo ezichaseneyo zokuxhobisa inkumbulo yemisebenzi yokuvuselela iimvakalelo [20, 26, 59]. Ihomoni zeAdrenal zaye zaququzelela ukudityaniswa kwemisebenzi evuselelayo ngokwasemphefumlweni ngokusebenzisana neendlela ezingekho mgangathweni kwi-basolateral amygdala [75]. Ngakumbi i-germane ukuya kwi-thesis yangoku, ukusebenza kweCRF kwi-basolateral amygdala ngokuthintela iprotheni ebopha i-CRF eveliswe ngokuqhubekisa ukuxhomekeka kwinadrenergic [76]. Ezi ziphumo zibonisa ukuba i-CRF inokudlala indima ekhethiweyo yokudibanisa iinkumbulo ezingapheliyo zamava axhokonxayo ngokomoya [76].
Ukudityaniswa kweenkqubo zoxinzelelo lobuchopho kumanqanaba amabini e-amygdala kunokubonelela ngesiseko esinyanzelekileyo sokuqhuba okuxhamleyo okufuna iziyobisi kubantu abaxhomekeke kubo. I-amygdala ye-basolateral ine-projektha enkulu kwi-nucleus esembindini ye-amygala. Ngokwedlule, kwimeko yoloyiko, iinkqubo zokudibanisa ziye zenziwa kwindawo ye-amygdala ye-basolateral, kwaye intetho yoloyiko sele ibonakalisiwe kwindawo yokuphuma kwe-amygdala: isentloko esisiseko se-amygdala. Ke ngoko, ukwenziwa kweCRF kunye neenkqubo ze-norepinephrine kuzo zombini i-nuspdala ye-amygdala kunye ne-basolateral amygdala kunokuphembelela imimandla emibini eyahlukeneyo enokuthi idibanise ukukhusela isizinda ngasinye: imeko yeemvakalelo engalunganga yokurhoxa okunamandla kunye nokuziqhelanisa nokuzikhusela kunye nokudityaniswa kwenkumbulo zokuvuselela iimvakalelo amava (Umzobo 4). Umzekelo, indawo ephambili ye-amygdala ibhalwe kakuhle kwiziphumo zobuchopho kwimimandla yengqondo, njenge-hypothalamus kunye nengqondo yobuchopho. Ngokuchaseneyo, i-basolateral amygdala yenzelwa imbonakalo yokudibanisa iinkumbulo zamava axhokonxayo ngokwasemoyeni nge-nucleus accumbens, i-caudate nucleus, hippocampus, kunye ne-entorhinal cortex [56]. Kwimeko yokwesaba, iintlobo ezimbini ezikhuphisanayo zokulungiswa kwengcaciso ngaphakathi kwi-amygdala ziye zathatyathwa ukuba zibandakanyeke ngexesha lokufunda. Kwimodyuli edityanisiweyo, ulwazi malunga nokhuthazo olunemeko kunye nokunganyanzelisi lungena kwaye lunxulunyaniswa ne-BLA, kwaye olu lwazi luhanjiswa kwi-nucleus esembindini ye-amygdala ngentetho yokoyika. Ngenye indlela, imodeli ehambelana nayo iphakamisa ukuba i-basolateral amygdala kunye ne-nucleus esembindini ye-amygdala zombini zenza imisebenzi yokudibanisa [98]. Ke, iinkqubo zehormon, noradrenergic, kunye neCRF zinokuphinda zenziwe ukuba zisebenze ziziphumo ezigwenxa zokurhoxiswa kweziyobisi ukwenza isiseko sogxininiso olubi oluqhuba ukuqhuba iziyobisi kunye neendlela ezinokubangela ukuqhubela phambili imeko yeemvakalelo ezinceda ukuqhuba imeko yobukhoboka ngokubanzi .
Imibulelo
Umbhali angathanda ukubulela uMichael Arends ngoncedo lwakhe ngokulungiselela lo mbhalo wesandla. Uphando luxhaswe liZiko leSizwe leZibonelelo zezeMpilo i-AA06420 kunye ne-AA08459 evela kwiZiko leSizwe ngokuSetyenziswa gwenxa kotywala, I-DA10072, i-DA04043, kunye ne-DA04398 kwiZiko leSizwe leSizwe ngokuSetyenziswa gwenxa kweziyobisi, kunye ne-DK26741 kwiZiko leSizwe leSifo seSwekile kunye nokuDakumba kunye neZifo zeNtso. Uphando lwaluxhaswe liziko lePearson loTywala kunye noPhando ngeziyobisi. Le yinombolo yokupapasha i19965 evela kwiZiko loPhando lweScript.
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