Mphamvu za maulendo a Neuronal oledzera, Mphoto, Antireward ndi Emotional Memory (2009)

Ndemanga: Koob ndi m'modzi mwa akatswiri padziko lapansi. Kafukufuku wake akuyang'ana pa "anti-mphotho" monga woyendetsa kupititsa patsogolo chizolowezi chobwerera ndikuyambiranso. Anti-mphotho amatanthauza njira zomwe zimapangitsa kuti munthu wosuta akhale wosasangalala kotero kuti amapewa zochitikazo pogwiritsabe ntchito.

Lumikizani ku Phunziro Lathunthu

George F. Koob, Ph.D.

Pharmacopsychiatry. 2009 May; 42 (Suppl 1): S32-S41.

Idasindikizidwa pa intaneti 2009 May 11. yesani: 10.1055 / s-0029-1216356.

George F. Koob, Komiti ya Neurobiology ya Addictive Disorders, The Scripps Research Institute, La Jolla California, USA;

Makalata: George F. Koob, Ph.D., Komiti Yoona za Matenda a Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA 92037, foni: 858-784-7062, fakisi: 858-784-7405, Imelo: [email protected]

Kudalirika

Kugwiritsa ntchito mankhwala osokoneza bongo kumaganiziridwa ngati kosatha, kubwereranso kugwiritsa ntchito mankhwala osokoneza bongo ndi vuto lalikulu la ubongo wa hedonic. Ntchito yogwiritsira ntchito mankhwala osokoneza bongo ikuphatikizapo kuchepa kwa ntchito za magulu a ubongo pofuna kulimbitsa mankhwala ndi kuwalimbikitsa za ubongo zomwe zimagwirizanitsa kusokoneza kolakwika. Zomwe zimagwiritsidwa ntchito pazitsulo zowonongeka ("mdima") zimaphatikizapo kuitanitsa zinthu zomwe amygdala amachititsa komanso maganizo a ubongo, kuphatikizapo corticotropin-release factor ndi norepinephrine. Kusintha kumeneku, kuphatikizapo kuchepa kwa mphoto, kumatsitsimikiziridwa kuti apitirize kukhala ngati chikhalidwe chokhazikika chomwe chimapangitsa kuti munthu ayambe kubwerera. Kubwereranso kumaphatikizapo mbali yayikulu ya amygdala yomwe ikutsogoleredwa poyambitsa zotsatira zotsitsimula zomwe zakhala zikugwirizanitsa ndi kufunafuna mankhwala ndi kusuta mankhwala. Amygdala yokhala ndi moyo wapadera imathandiza kwambiri pokonzekera kukumbukira maganizo. Lingaliro lofotokozera apa ndilokuti machitidwe opanikizika a ubongo omwe amachititsidwa ndi zotsatira zokakamiza za kuchotsa mankhwala sizingangowonjezera zokhazokha zomwe zimayambitsa mankhwala osokoneza bongo, komabe komanso njira zothandizana nazo zomwe zimapangitsa kuti maganizo awo apitirire komanso kuthandizira kuthetsa vutoli.

Makhalidwe Abwino

Kuledzera ndi mankhwala osokoneza bongo, komwe kumadziwikanso kuti kudalira mankhwala osokoneza bongo, ndi vuto lomwe limabweranso nthawi zonse lomwe limadziwika ndi (1) kukakamiza kufunafuna ndi kumwa mankhwalawo, (2) kulephera kudziletsa pakuchepetsa kumwa, ndi (3) kuonekera kwa mkhalidwe woipa wamaganizo (monga dysphoria, nkhawa, kukwiya) pamene mwayi wopeza mankhwalawo waletsedwa (womwe wafotokozedwa pano ngati kudalira). Ngakhale kuonekera kwa mkhalidwe woipa wamaganizo si muyezo wokhazikika wa Kudalira Mankhwala Omwe afotokozedwa ndi Diagnostic and Statistical Manual of Mental Disorder , kope ^lachinayi (DSM-IV, [ 4 ]), ndi chiwonetsero cha zomwe zatchedwa kusiya kukakamiza. Motero, ndi muyezo umodzi mu DSM-IV ndipo ndi chizindikiro chofala cha kuledzera [ 78 ]. Mwachipatala, kugwiritsa ntchito mankhwala osokoneza bongo nthawi zina koma pang'ono ndikosiyana ndi kugwiritsa ntchito mankhwala osokoneza bongo mokakamiza komanso kuonekera kwa kuledzera kwa mankhwala osokoneza bongo nthawi yayitali. Cholinga chofunikira cha kafukufuku wamakono wa neurobiological ndikumvetsetsa njira za neuropharmacological ndi neuroadaptive mkati mwa ma neurocircuits enaake omwe amathandizira kusintha kuchoka pa kugwiritsa ntchito mankhwala osokoneza bongo nthawi zina, komanso kutayika kwa ulamuliro wamakhalidwe pakufuna mankhwala osokoneza bongo ndi kumwa mankhwala osokoneza bongo omwe amatanthauza kuledzera kosatha. Kuledzera kwa mankhwala osokoneza bongo kwaonedwa ngati vuto lomwe limayamba kuchoka pa kusachita zinthu mopitirira muyeso kupita ku kukakamizidwa mu chizolowezi cholephera chomwe chili ndi magawo atatu: kuganizira/kuyembekezera, kuledzera kwambiri, ndi kusiya/kusokoneza [ 41 , 44 , 45 ].

Malingaliro osiyanasiyana a chiphunzitso, kuyambira pa psychology yoyesera ndi ya anthu mpaka neurobiology, akhoza kuyikidwa pamwamba pa magawo atatu awa, omwe amaganiziridwa kuti amadyana, kukhala olimba kwambiri, ndikusintha kuchoka pa zabwino kupita ku zolimbikitsa zoipa. Kulimbitsa kwabwino kungatanthauzidwe ngati mkhalidwe momwe kuwonetsa kwa cholimbikitsa kumawonjezera mwayi woyankha, ndipo kulimbitsa koyipa kungatanthauzidwe ngati mkhalidwe momwe kuchotsa cholimbikitsa kumawonjezera mwayi woyankha. Ma substrates a mitsempha ya makhalidwe abwino olimbikitsa kumwa mankhwala osokoneza bongo ndi kufunafuna mankhwala osokoneza bongo akhala akulamulira gawo la neurobiology ya chizolowezi. Komabe, ntchito yaposachedwa yayang'ana kwambiri njira zoyipa zolimbikitsira zomwe zimagwirizanitsidwa ndi kuchotsa mkhalidwe woyipa wamalingaliro wokhudzana ndi kudziletsa komanso kudziletsa kwakanthawi kwa gawo la kuchotsedwa/kukhudzidwa koyipa ndi gawo lotanganidwa/loyembekezera la chizolowezi, motsatana [ 34 , 37 ]. Ndondomeko ya malingaliro imachokera ku mbali "zolimbikitsa" za chizolowezi choledzera komanso kutsindika kusintha kuchoka pa kugwiritsa ntchito mankhwala osokoneza bongo kupita ku chizolowezi chomwe chimayambitsa vuto la maganizo (monga dysphoria, nkhawa, kukwiya; yotchedwa "mbali yamdima") pamene mwayi wopeza mankhwalawo waletsedwa ndipo umapereka maziko ofunikira olimbikitsira kukhazikika kwa chizolowezicho ndikupitirizabe.

Ma circuits awiri a neurobiological akuganiziridwa kuti ndi ofunikira kwambiri pa zinthu zokhudzana ndi hedonic zomwe zimapangitsa munthu kufuna mankhwala osokoneza bongo: ma circuits a neurobiological omwe amakhudzidwa ndi kusokonekera kwa mphamvu zabwino zolimbitsa thupi za mankhwala osokoneza bongo (ventral striatal-pallidal-thalamic loops) ndi ma circuits a neurobiological omwe amagwirizanitsidwa ndi kulembedwa kwa mphamvu zoipa zolimbitsa thupi za mankhwala osokoneza bongo (amygdala yowonjezera) ( Chithunzi 1 ). Ndemangayi ifufuza njira za neurobiological za chizolowezi zomwe zimakhudzidwa m'magawo osiyanasiyana a chizolowezi, poyang'ana kwambiri kusinthasintha kwa ma neurocircuits okhudzana ndi kusintha kuchokera ku kumwa mankhwala osokoneza bongo kupita ku chizolowezi cha mankhwala osokoneza bongo, zotsatira zolimbikitsa za kusiya ndi kusiya nthawi yayitali, komanso kufanana ndi kukumbukira kwamalingaliro komwe kumathandiza kupitiriza njira yoledzera.

Mabwalo ozungulira a Neural omwe amagwirizanitsidwa ndi magawo atatu a kusokoneza bongo, mankhwala omwe akugwiritsidwa ntchito pakulandila pazitsamba izi, ndi zolinga zomwe zatchulidwa mu ndemangayi zokhudzana ndi magawo awa. Kuledzeretsa / kuledzeretsa siteji: Kulimbikitsanso ...

Neurocircuitry of Positive Reinforcement yomwe imayikidwa ndi mankhwala osokoneza bongo

Dongosolo la mphotho ya ubongo lakhala likuganiziridwa kwa nthawi yayitali kuyambira pomwe adapeza mphotho yamagetsi yolimbikitsa ubongo kapena kudzilimbikitsa mkati mwa ubongo [ 64 ] komanso kupeza kuti nyama zimadzipatsa mankhwala okha popanda mbiri yodalira [ 81 ]. Mphotho yolimbikitsa ubongo imaphatikizapo ma neurocircuitry ambiri mu ubongo, koma malo ofunikira kwambiri omwe amafotokozedwa ndi malire otsika kwambiri a mphotho amakhudza njira ya medial forebrain bundle yolumikiza dera la ventral tegmental ndi basal forebrain [ 64 ]. Ngakhale kuti poyamba chidwi chachikulu chinali pa ntchito ya ascending monoamine systems mu medial forebrain bundle, machitidwe ena osapanga dopaminergic mu medial forebrain bundle ali ndi gawo lofunika kwambiri [ 27 ]. Kugwirizana kwa mankhwala osokoneza bongo ndi dongosolo la mphotho loganiziridwa kunagogomezeredwa ndi kuwona kuti mankhwala onse osokoneza bongo, akaperekedwa mwachangu, amachepetsa malire a mphotho yolimbikitsa ubongo [ 47 ].

Kuwongolera kwakukulu kwa mankhwala osokoneza bongo kumayendetsedwa ndi kukhazikitsidwa kwa dopamine, serotonin, peptides opioid, ndi njira za γ-aminobutyric acid (GABA), mwazochita zozizwitsa ku basal forebrain (makamaka nucleus accumbens ndi chigawo chapakati cha amygdala ) kapena mwachindunji m'dera la ventral tegmental [32, 35, 42, 61]. Umboni wochuluka umagwirizana ndi lingaliro lakuti masolimbic dopamine dongosolo likuyendetsedwa kwambiri ndi mankhwala a psychostimulant panthawi yochepa-yopindula yokhazikika. Ngakhale kuti jekeseni wa mankhwala osokoneza bongo amachulukitsa kuchuluka kwa dopamine m'magulu a nucleus accumbens mu vivo microdialysis [14], kucheperapo kwakukulu kumachitika mu nucleus accumbens kwa ethanol, chikonga, ndi opioids panthawi ya kudzilamulira [15, 97]. Kuonjezera apo, ma opioid ndi ethanol okha-administration administration sakukhudzidwa ndi chiwonongeko chosankha cha masolambic dopamine system [16, 60, 66, 69]. Machitidwe a Serotonin, makamaka omwe amaphatikizapo serotonin 5-HT_1B kulandirira kulandirira mu nucleus accumbens, komanso kumakhudzidwa kwambiri ndi kuwonjezereka kwa mankhwala a psychostimulant. Opioid peptide receptors mu ventral striatum, ventral tegmental dera, ndipo amygdala akhala akugwiritsidwa ntchito kuti agwirizane ndi mphamvu yowonjezera ya opioid ndi ethanol kudzilamulira, makamaka pogwiritsa ntchito zotsatira za opioid antagonists. Otsutsana ndi opioid adayikidwa mu nucleus accumbens ndi pakatikati a amygdala ndi othandiza kwambiri pofuna kuteteza opioid ndi ethanol self-administration [28, 92]. Machitidwe a GABAergic amavomerezedwa musanayambe kutsatizana ndi amygdala ndi ethanol pa mankhwala osokoneza bongo, ndipo a GABA amalowetsedwa mu amygdala block ethanol self-administration (kwa ndemanga, onani [35, 61]).

Ma substrates a mitsempha ndi njira za neuropharmacological zomwe zimayambitsa zotsatira zoyipa zosiya kugwiritsa ntchito mankhwala osokoneza bongo zitha kusokoneza machitidwe omwewo a neurochemical ndi ma neurocircuits omwe amakhudzidwa ndi zotsatira zabwino zolimbikitsa za mankhwala osokoneza bongo, zomwe zimatchedwa neuroadaptation yamkati mwa dongosolo. Mankhwala onse osokoneza bongo amabweretsa kukwera kwa malire a mphotho ya ubongo panthawi yosiya mwachangu [ 43 ], ndipo m'mitundu ya nyama yomwe yasintha kukhala chizolowezi, kuwonjezeka kwa malire a mphotho ya ubongo (mwachitsanzo, kuchepa kwa mphotho) kumayamba pang'onopang'ono ndipo kumagwirizana kwambiri ndi kuwonjezeka kwa kumwa mankhwala osokoneza bongo ndi mwayi wowonjezera [ 1 , 31 ] ( Chithunzi 2 ).

(A) Kuyanjana pakati pa kukwera m'maso mwachangu (ICSS) kulipira malire ndi cocaine kudya. (kumanzere) Kusintha kwa peresenti kuchokera kumbali yoyamba ya ICSS. (Chabwino) Chiwerengero cha jekeseni wa cocaine chinaperekedwa pa ola loyamba la aliyense ...

Pa nthawi yopuma mwadzidzidzi, kuchepa kwa ntchito ya mesocorticolimbic dopamine system kumachitika, komanso kuchepa kwa ntchito yogwira ntchito mu opioid peptide, GABA, ndi glutamate systems mu nucleus accumbens ndi amygdala. Kupereka mobwerezabwereza kwa psychostimulants kumapangitsa kuti dopamine ndi glutamate neurotransmission ziyambe kugwira ntchito mu nucleus accumbens [ 91 , 96 ]. Komabe, kupereka nthawi yayitali kumabweretsa kuchepa kwa dopaminergic ndi glutamatergic neurotransmission mu nucleus accumbens panthawi yopuma mwadzidzidzi [ 29 , 97 ], mayankho osiyana a opioid receptor transduction mechanisms mu nucleus accumbens panthawi yopuma mwadzidzidzi [ 84 ], kusintha kwa GABAergic neurotransmission panthawi yopuma mowa [ 25 , 71 ], ndi kusintha kwapadera kwa nicotinic acetylcholine receptor function panthawi yopuma mowa.

Kafukufuku wa anthu wokhudza anthu omwe ali ndi vutoli panthawi yosiya kumwa mankhwala osokoneza bongo kapena nthawi yayitali yosiya kumwa mankhwala osokoneza bongo wapereka zotsatira zomwe zikugwirizana ndi maphunziro a nyama. Ma receptors a Dopamine D2 _amachepa (oganiziridwa kuti awonetse momwe hypodopaminergic imagwirira ntchito), ndipo hypoactivity ya orbitofrontal-infralimbic cortex system imachitika [ 95 ]. Kuchepa kwa ntchito ya neurotransmitter yolandira mphotho kwaganiziridwa kuti kumathandizira kwambiri mkhalidwe woipa wokhudzana ndi kusiya kumwa mankhwala osokoneza bongo ndipo kungayambitse kusintha kwa nthawi yayitali kwa biochemical komwe kumathandizira ku matenda amisala a kudziletsa kwakanthawi komanso chiopsezo chobwereranso.

Matenda a Neurocircuitry a Negative Reinforcement Ogwirizana ndi Kusagwiritsira Ntchito Mankhwala Osokoneza Bongo Osatha

Mbali yakuda ya chizolowezi [ 43 ] yaganiziridwa kuti ikuphatikizapo pulasitiki ya nthawi yayitali, yopitilira mu ntchito ya ma neural circuits omwe amayang'anira machitidwe olimbikitsa omwe amachokera ku kusonkhanitsa machitidwe oletsa mphotho omwe amachititsa kuti zinthu zisinthe. Gawo la kukhudzidwa kochoka/kuipa lomwe lafotokozedwa pamwambapa lili ndi zinthu zofunika kwambiri zolimbikitsa, monga kukwiya kosatha, kupweteka kwamaganizo, kutopa, dysphoria, alexithymia, ndi kutayika kwa chilimbikitso cha mphotho zachilengedwe, ndipo limadziwika mwa nyama ndi kuwonjezeka kwa malire a mphotho panthawi yosiya mankhwala onse akuluakulu ozunza. Kuletsa mphotho ndi lingaliro lozikidwa pa lingaliro lakuti machitidwe a ubongo alipo kuti achepetse mphotho [ 41 , 45 ].

Chiwalo cha neuroanatomical chotchedwa amygdala yowonjezereka chikhoza kuyimira gawo la neuroanatomical chifukwa cha zotsatira zoyipa pa ntchito ya mphotho yomwe imatanthauzidwa kuti antireward. Amygdala yowonjezereka imapangidwa ndi nucleus ya stria terminalis, nucleus yapakati ya amygdala, ndi malo osinthira m'chigawo chapakati cha nucleus accumbens (chipolopolo cha nucleus accumbens). Chigawo chilichonse chili ndi kufanana kwa cytoarchitectural ndi circuitry. Gawo lapakati la amygdala yowonjezereka limalandira ma afferent ambiri kuchokera ku limbic structures, monga basolateral amygdala ndi hippocampus, ndipo limatumiza ma efferents ku gawo lapakati la ventral pallidum ndi lateral hypothalamus, motero kutanthauzira kwambiri madera enieni a ubongo omwe amalumikiza kapangidwe ka limbic (maganizo) ndi extrapyramidal motor system [ 2 ].

Machitidwe a neurochemical mkati mwa amygdala yowonjezereka yomwe imapereka maziko a neurochemical a antireward ikhoza kukhala yayikulu ndipo imasonyeza dongosolo lovuta lokhazikika kuti likhalebe ndi hedonic homeostasis [ 41 ]. Komabe, malo ofunikira a neurochemical a machitidwe a neurotransmitter antireward ndi corticotropin-releasing factor (CRF), norepinephrine, ndi dynorphin. CRF, norepinephrine, ndi dynorphin zimatengedwa panthawi yomwe munthu akumwa mankhwala osokoneza bongo, zomwe zimapangitsa kuti munthu azivutika maganizo kapena azivutika maganizo akasiya kumwa mankhwala [ 36 , 45 ].

Machitidwe osiyanasiyana a mitsempha omwe amagwira ntchito yosintha kupsinjika angagwirenso ntchito mkati mwa mitsempha ya mitsempha ya mitsempha ya mitsempha ya ubongo pofuna kuthana ndi kupezeka kosatha kwa mankhwala osokoneza bongo ndikubwezeretsa ntchito yabwino ngakhale kuti pali mankhwala - otchedwa neuroadaptation pakati pa dongosolo. Hypothalamic-pituitary-adrenal axis ndi ubongo stress system, zonse zomwe zimayendetsedwa ndi CRF, zimasokonekera chifukwa cha kupereka mankhwala osokoneza bongo kosatha, ndi yankho lofala la adrenocorticotropic hormone ndi corticosterone ndi amygdala CRF yowonjezereka panthawi yosiya mankhwala onse akuluakulu osokoneza bongo [ 43 , 48 ]. Kusiya kugwiritsa ntchito mankhwala osokoneza bongo kungawonjezere kutulutsidwa kwa norepinephrine mu nucleus ya stria terminalis ndikuchepetsa kuchuluka kwa neuropeptide Y (NPY) mu amygdala [ 65 , 77 ].

Mwachitsanzo, mowa, CRF ikhoza kukhala ndi mbali yofunikira pakuyanjanitsa njira zothandizira anthu kuti azitha kuvutika maganizo komanso nkhawa zomwe zimayambitsa kumwa mowa mwauchidakwa [40]. Zigawo za amygdala (kuphatikizapo pakatikatikati ya amygdala) zili ndi mapepala akuluakulu a CRF, maselo, ndi mapulogalamu okhudzidwa ndipo amaphatikizapo mbali ya "extrahypothalamic" CRF-stress system [57]. Kafukufuku wambiri akuwonetsa kuti mbali ya amygdala CRF ikugwira nawo ntchito potengera mayankho a makhalidwe omwe akukhudzana ndi mantha ndi nkhawa [40]. Panthawi ya kutulutsa mafuta m'thupi, extrahypothalamic CRF mawonekedwe amakhala oopsa, ndi kuchuluka kwa CRF extracellular mkatikatikati mwa amygdala ndi bedi la stria terminalis ya makoswe odalira [19, 58, 65, 99], ndipo kusokoneza uku kwa machitidwe a CRF a ubongo kumagwiritsidwa ntchito poyang'anira zonse zomwe zimapangitsa kuti azikhala ndi nkhawa monga momwe amachitira komanso kupititsa patsogolo ubweya wa ethanol wokhudzana ndi kutaya kwa ethanol. Pogwirizana ndi mfundo imeneyi, otsutsana ndi CRF a-helical CRF_9-41 ndi d-Inde CRF_12-41 (intracerebroventricular administration) amachepetsa zonse zomwe zimapangitsa kuti asakhale ndi nkhawa komanso khalidwe la ethanol,5, 93]. Otsutsana ndi CRF amapezeranso khalidwe lachisokonezo [68] komanso ethanol kudzilamulira pa makoswe odalira mafuta [19]. Kukonzekera koyenera kwa CRF₁ Otsutsana amachitanso zomwezo pa nkhawa monga mayankho okhudzana ndi kudziletsa kwapadera komanso mosakhalitsa komanso podziteteza pa ethanol panthawi yochotsa mofulumira ndikusiya kudziletsa [36]. Deta iyi imasonyeza udindo wofunikira kwa CRF, makamaka mkatikatikati mwa chigawo cha amygdala, pakuyanjanitsa kuwonjezereka kwaumwini komwe kumakhudzana ndi kudalira. Zotsatira zofananazi zakhala zikuwonedwa ndi kuchulukitsidwa kwadzidzidzi kokhazikika kwazomwe zikugwirizana ndi kupititsa patsogolo kwa heroin [24], cocaine [85], ndi chikonga [21].

Zotsatirazi sizikusonyeza kusintha kokha kwa ntchito ya ma neurotransmitters okhudzana ndi zotsatira zolimbikitsa kwambiri za mankhwala osokoneza bongo panthawi ya kukula kwa kudalira, monga kuchepa kwa dopamine, ma opioid peptides, serotonin, ndi ntchito ya GABA, komanso kulembedwa kwa CRF system ( Chithunzi 3 ). Kusinthidwa kwina pakati pa dongosolo komwe kumakhudzana ndi kusiya kukakamiza kumaphatikizapo kuyambitsa dynorphin/κ opioid system, kuyambitsa norepinephrine brain stress system, ndi kusokonekera kwa NPY brain antistress system [ 43 ]. Kuphatikiza apo, kuyambitsa machitidwe a kupsinjika kwa ubongo kungathandize osati kokha ku mkhalidwe woipa wokhudzana ndi kusiya kukakamiza, komanso kufooka kwa zopsinjika zomwe zimawonedwa panthawi yosiya kwa nthawi yayitali mwa anthu. Maphunziro onsewa a neurochemical (kuchokera ku chizolowezi cha neurobiology) ndi maphunziro a neuroanatomical (kuchokera ku khalidwe la neuroscience) akuwonetsa gawo lolemera lophatikizana ndi zolimbikitsa zamaganizo zokhudzana ndi "mbali yakuda ya chizolowezi," zomwe zimatanthauzidwa ngati chitukuko cha mkhalidwe wotsutsa womwe umayambitsa kulimbitsa koyipa kwa chizolowezi.

Matendawa amagwiritsa ntchito mankhwala osokoneza bongo omwe amachititsa kuti anthu azizunzidwa komanso kuti asamangodalira kwambiri momwe amachitira. Zinthu zazikulu za mphotho ...

Chizolowezi ndi Antireward: Mantha ndi Zowawa

Mfundo ina yokhutiritsa yokhudza kuphatikiza kwa amygdala ndi momwe zimakhalira m'maganizo imachokera ku deta yochuluka yochokera kwa Le Doux ndi anzake, omwe asonyeza kugwirizana kwa mawu a mantha omwe ali mu mtima wapakati wa amygdala [ 50 ]. Kafukufuku wokhudza kayendedwe ka mitsempha ya mitsempha ya mantha akuwonetsa kuti zolimbikitsa kumva kuchokera ku cortex ya mawu ndi ululu wochokera ku cortex ya somatosensory zimakumana pa amygdala ya lateral, yomwe kenako imapita ku mtima wapakati wa amygdala kuti ipange mayankho osiyanasiyana a autonomic ndi khalidwe ku mantha omwe ali mumtima [ 50 ]. Mwina chochititsa chidwi kwambiri ndi lingaliro lakuti mtima wapakati wa amygdala ndi gawo lofunika kwambiri la mitsempha yomwe imakhudzidwa ndi kukonza ululu wamaganizo [ 67 ]. Njira ya spino (trigemino)-ponto-amygdaloid yomwe imachokera ku dorsal horn kupita ku dera la mesencephalic parabrachial kupita ku mtima wapakati wa amygdala yaganiziridwa kuti imagwira ntchito mu kukonza ululu wamaganizo [ 7 ]. Pansi pa dongosololi, ululu umayimira kusweka kwa njira zowongolera ubongo zomwe zimayang'anira nociception.

Mavuto omwe ma opioid amachititsa kuti ululu ukhale wovuta komanso kubwezeretsa malo otsekemera amakhala mavuto omwe opioid amachepetsa kupweteka ndikubwezeretsanso phunzirolo ku homeostatic hedonic state; Choncho, njira zotsutsana siziyenera kuchitidwa. Komabe, ngati opioid yochulukitsidwa imaperekedwa, mwina chifukwa cha kusintha kwakukulu kapena mankhwala osokoneza bongo, thupi lidzachitapo kanthu potsutsana ndi zomwe zikugwirizana ndi otsutsa. Hyperalgesia kwa opioids ikhoza kuchitika mu nkhani zomwe opioid ngokha imapuma ndi homeostasis. Hyperalgesia sizingatheke pamene opioid ikubwezeretsanso homeostasis. Kubwereza kumagwirizanitsa ntchito zotsutsana popanda nthawi kuti dongosolo lokhazikitsanso homeostasis lizitha kugwira ntchito osati hyperalgesia yekha komanso ndondomeko yotsatiridwa yomwe ili pansipa. Njira zoterezi zingapangidwe pochita ndi opioid kwambiri, kuchiza ndi opioid pamene mlingo umatha kupweteka chifukwa cha mankhwala a pharmacokinetic, ndi / kapena kukambirana nkhani imene palibe kwenikweni ululu ulipo (Koob GF, Shurman J, Gutstein H, zotsatira zosasindikizidwa).

Kuchotsa, Kutaya Nthawi Zonse, ndi Allostasis

Kukula kwa mkhalidwe woipa wamaganizo womwe umayambitsa kulimbitsa koipa kwa chizolowezi kwatanthauzidwa ngati "mbali yakuda" ya chizolowezi [ 43 , 45 ] ndipo kumaganiziridwa kuti ndi gawo loyambitsa kuchotsedwa kwa chilimbikitso cha mphamvu ya hedonic yomwe imadziwika kuti njira yotsutsa pamene zotsatira zoyamba za mankhwala zimakhala zosangalatsa. Mkhalidwe woipa wamalingaliro womwe umaphatikizapo gawo la kuchotsedwa/kukhudzidwa koipa komwe kwafotokozedwa pamwambapa uli ndi zinthu zofunika kwambiri zolimbikitsa, monga kukwiya kosatha, kupweteka kwamaganizo, malaise, dysphoria, alexithymia, ndi kutayika kwa chilimbikitso cha mphotho zachilengedwe mwa anthu, ndipo zimawonetsedwa m'mitundu ya nyama mwa kuwonjezeka kwa khalidwe longa nkhawa, mayankho ofanana ndi dysphoric, ndi malire a mphotho panthawi yosiya mankhwala onse akuluakulu ozunza. Monga taonera pamwambapa, njira ziwiri zimaganiziridwa kuti zipange maziko a neurobiological a kuchotsedwa kwa chilimbikitso: kutayika kwa ntchito m'machitidwe opatsa mphotho (mkati mwa dongosolo la neuroadaptation) ndi kusonkhanitsa kupsinjika kwa ubongo kapena machitidwe oletsa mphotho (pakati pa dongosolo la neuroadaptation) [ 38 , 41 ]. Pamene kudalira ndi kusiya zinthu kukukula, machitidwe opsinjika maganizo muubongo monga CRF, norepinephrine, ndi dynorphin amatengedwa, zomwe zimapangitsa kuti zinthu zikhale ngati zosokoneza maganizo kapena zosokoneza maganizo [ 45 ]. Nthawi yomweyo, mkati mwa magawo olimbikitsa a amygdala yowonjezereka ya ventral striatum, ntchito yolandira mphotho imachepa. Kuphatikiza kwa kuchepa kwa ntchito ya neurotransmitter yolandira mphotho ndi kulembetsa machitidwe oletsa mphotho kumapereka gwero lamphamvu la mphamvu zoyipa zomwe zimapangitsa kuti munthu azitsatira mankhwala osokoneza bongo komanso azizolowera.

Mutu wonse wa chidziwitso womwe umatchulidwa apa ndi wakuti kumwa mowa mwauchidakwa kumaimira kupuma ndi homeostatic njira zogwiritsira ntchito ubongo zomwe zimayendetsa chikhalidwe cha nyama. Komabe, lingaliro lakuti kumwa mowa mwauchidakwa kumaimira kuphweka kosavuta ndi homeostasis sikokwanira kufotokoza zinthu zingapo zofunika kwambiri. Kugwiritsa ntchito mankhwala osokoneza bongo, mofanana ndi mavuto ena a thupi monga kuthamanga kwambiri kwa magazi, kuwonjezereka kwa nthawi, kumakhudzidwa ndi zochitika zowononga zachilengedwe, ndipo amasiya njira yotsalira yomwe imalola kuti "kubwereranso" mofulumira ngakhale miyezi ndi zaka pambuyo pochotsedwa ndi kudziletsa. Kubwereranso, kapena kubwereranso kwa mankhwala osokoneza bongo pambuyo pa nthawi ya kudziletsa, ndi imodzi mwa mfundo zomwe zimadalira kumwa mowa. Kukula kwa kudalira kwatchulidwa kuti kuthandizira kwambiri pakukonzekera kugwiritsidwa ntchito mobwerezabwereza ndi kubwereranso pakapita nthawi.

Mwa anthu omwe ali ndi mowa, zizindikiro zambiri zomwe zimadziwika ndi malingaliro oipa zimapitirira nthawi yayitali atasiya kumwa mowa mwachangu. Zizindikirozi, zomwe zimachitika munthu akasiya kumwa mowa kwambiri, zimakhala ndi malingaliro oipa komanso zimakhala zochepa ndipo nthawi zambiri zimayamba kubwereranso. Maganizo oipa, kuphatikizapo malingaliro oipa monga mkwiyo, kukhumudwa, chisoni, nkhawa, ndi liwongo, ndizomwe zimayambitsa kubwereranso [ 53 ]. Mkhalidwewu umatchedwa "kudziletsa kwa nthawi yayitali" ndipo wafotokozedwa mwa anthu omwe ali ndi Hamilton Depression rating ≥8 ndi zinthu zitatu zotsatirazi zomwe zimawonedwa nthawi zonse ndi anthu: kupsinjika maganizo, nkhawa, ndi liwongo [ 53 ]. Mwachitsanzo, kutopa ndi kupsinjika kwanenedwa kuti kumapitirira mpaka milungu 5 munthu atasiya kumwa [ 3 ]. Nkhawa zawonetsedwa kuti zikupitirira mpaka miyezi 9 [ 73 ], ndipo nkhawa ndi kupsinjika maganizo zawonetsedwa kuti zikupitirira mpaka 20-25% ya oledzera kwa zaka ziwiri atasiya kumwa mowa.

Ntchito ya nyama yokhala ndi kudalira mowa yawonetsa kuti kudalira mowa kale kumatha kuchepetsa "mlingo wodalira" kotero kuti nyama zomwe kale zinkadalira mowa zimasonyezanso zizindikiro zodzipatula kwambiri komanso nkhawa kuposa magulu omwe amamwa mowa koyamba [ 6 , 8 ]. Izi zikugwirizana ndi lingaliro lakuti kumwa mowa komanso kukula kwa kudalira mowa makamaka kungayambitse kusintha kosatha pakuyankha mowa. Komabe, kubwereranso nthawi zambiri kumachitika ngakhale zizindikiro zosiya mowa mwachangu zitatha, zomwe zikusonyeza kuti kusintha kwa neuropharmacological komwe kumachitika panthawi yodalira mowa kumatha kupitirira zizindikiro zomaliza zoonekeratu za kusiya mowa ("protracted motivational withdrawal syndrome"). Kusiya mowa kwa nthawi yayitali kumeneku kuli ndi tanthauzo lolimbikitsa. Mbiri ya kudalira makoswe ndi mbewa imatha kubweretsa kukwera kwa nthawi yayitali kwa kudzilamulira kwa ethanol m'magawo a tsiku ndi tsiku a mphindi 30 nthawi yayitali atasiya kumwa mowa mwachangu komanso kuchotsa poizoni m'thupi [ 70 , 72 ]. Kuwonjezeka kwa kudzilamulira kumaphatikizidwanso ndi kuyankha kwa khalidwe ku zinthu zomwe zimakuvutitsani komanso kuyankha kwa CRF receptor antagonists [ 46 ]. Kusintha kosalekeza kwa kudzilamulira kwa ethanol komanso kukhudzidwa kotsalira kwa zinthu zopsinjika kumatha kufotokozedwa mwachisawawa ngati mkhalidwe wa "kudziletsa kwa nthawi yayitali." Kudziletsa kwa nthawi yayitali m'makoswe kumatenga nthawi yayitali pambuyo poti kusiya mwachangu kwatha pamene kuchuluka kwa ethanol m'thupi kuposa momwe zimakhalira kale komanso kuyankha kwamphamvu kwa kupsinjika kumapitilira (masabata 2-8 pambuyo posiya kumwa ethanol nthawi yayitali). Kuwonjezeka kosalekeza kwa kudzilamulira kwa mankhwala panthawi yosiya kumwa kwa nthawi yayitali kwaganiziridwa kuti kumaphatikizapo kusintha kofanana ndi allostatic kotero kuti malo okhazikika a mphotho ya mankhwala amakwezedwa (kulekerera kwa hedonic) [ 42 ]. Makhalidwe awa a chizolowezi cha mankhwala osokoneza bongo amatanthauza zambiri osati kungokhala kusokonekera kwa homeostatic kwa ntchito ya hedonic ndi ntchito yayikulu, koma kusweka kwamphamvu ndi homeostasis ya machitidwe awa omwe amatchedwa allostasis.

Allostasis, yomwe poyamba inkaganiziridwa kuti ifotokoze matenda osatha a ntchito yodziyimira payokha komanso yodziyimira payokha, imatanthauzidwa kuti "kukhazikika kudzera mu kusintha" [ 86 ]. Allostasis imaphatikizapo njira yoperekera chakudya m'malo mwa njira zobwezera zoyipa za homeostasis, ndi kuwunikanso kosalekeza kwa zosowa ndikusintha kosalekeza kwa magawo onse kupita ku mfundo zatsopano. Chifukwa chake, njira yeniyeni ya thupi yomwe imalola mayankho mwachangu ku zovuta zachilengedwe imakhala injini ya matenda ngati nthawi yokwanira kapena zinthu sizikupezeka kuti zitseke yankho (monga, kuyanjana pakati pa CRF, norepinephrine, ndi dynorphin mu basal forebrain zomwe zingayambitse nkhawa ndi dysphoria) [ 33 ]. Njira zosinthira zaganiziridwanso kuti zimagwira ntchito pakusunga dongosolo la malingaliro a ubongo lomwe limagwira ntchito pa matenda a chizolowezi [ 42 ]. Zigawo ziwiri zomwe zimaganiziridwa kuti zikufotokoza za mkhalidwe woipa wamalingaliro wokhudzana ndi chizolowezi ndi kuchepa kwa ntchito ya ma transmitter a mphotho ya ubongo ndi ma circuits ndi kulembetsa machitidwe a antireward kapena stress muubongo ( Chithunzi 3 ). Mavuto obwerezabwereza, monga momwe zimakhalira ndi mankhwala osokoneza bongo, amachititsa kuti ubongo uyese kusintha kwa mamolekyulu, ma cell, ndi ma neurocircuitry kuti ukhalebe wolimba koma pamtengo wotsika. Mtengo wake ndi kuipiraipira kwa mkhalidwe woipa wamaganizo panthawi yosiya mwadzidzidzi komanso kwa nthawi yayitali ndipo ukugwirizana ndi tanthauzo la katundu wolemera [ 54 ]. Pa dongosolo la chizolowezi cha mankhwala osokoneza bongo lomwe lafotokozedwa pano, mkhalidwe wotsalira wamaganizo woipa umaonedwa ngati mkhalidwe wolemera [ 42 ]. Lingaliro losangalatsa lomwe lingafotokozedwe pansipa ndilakuti machitidwe omwewo amalingaliro omwe amagwiritsidwa ntchito poyankha "nkhondo kapena kuthawa" angatenge nawo gawo pophatikiza zikumbukiro zokhudzana ndi chizolowezi.

Kusokoneza Bongo, Kuchokera Kumtima, ndi Kukumbukira Maganizo

Umboni wambiri umasonyeza kuti mankhwala osokoneza bongo, komanso makamaka mankhwala osokoneza bongo, amatha kupititsa patsogolo chidziwitso. Zotsatira zoterezi zingaphatikizepo zochita pa malingaliro, chidwi, kuwukitsidwa, ndi kuwalimbikitsa, komanso kuphunzira ndi kukumbukira. Komabe, mwinanso chofunika kwambiri pa matenda a ubongo, kugwiritsa ntchito mankhwala osokoneza bongo kungasinthe kukumbukira zabwino ndi zoipa zolimbikitsa zotsatira za mankhwala. Chodabwitsa kwambiri ndi chakuti kukumbukira mankhwala kumakhala ndi gawo lina lapadera lomwe limapereka chitsimikizo chapadera pazokumbukilo zoterezi. Lingaliro limene lingaganizidwe apa ndilokuti mazenera a neural a mbali yakuda ya chizolowezi choledzeretsa amapezeka mofanana ndi zigawo za neural za memory "memory".

Umboni wambiri wochokera ku maphunziro a anthu ndi nyama umathandizira lingaliro lakuti mankhwala osokoneza bongo amatha kupereka mphamvu zolimbitsa thupi zomwe zimakhazikika komanso mphamvu zolimbitsa thupi zomwe zimakhazikika. Zitsanzo za nyama zomwe zimafuna mankhwala osokoneza bongo komanso kubwereranso m'thupi zimapitilira kupangidwa ndi kukonzedwanso, koma mpaka pano zakhala zikuwonetsa magwero achiwiri a mphamvu monga mphamvu yolimbitsa thupi [ 52 , 87 ]. Cholimbitsa thupi chomwe chimakhazikika chingatanthauzidwe ngati cholimbikitsa chilichonse chomwe chimapeza mphamvu zolimbitsa thupi kudzera mu mgwirizano ndi cholimbitsa thupi chachikulu. Mu njira yolimbitsa thupi yomwe imakhudzana ndi kudzipatsa mankhwala, anthu amaphunzitsidwa m'bokosi logwira ntchito lomwe lili ndi ma levers awiri momwe mayankho pa lever imodzi amachititsa kuti pakhale chilimbikitso chachifupi chotsatiridwa ndi jakisoni wa mankhwala (lever yogwira ntchito), ndipo mayankho pa lever ina alibe zotsatirapo panthawi yonse yoyesera (lever yosagwira ntchito; [ 12 , 82 ]). Pambuyo pake, kuthekera kwa chilimbikitso chomwe chinalipo kale, cholumikizidwa ndi mankhwala kuti chipitirize kuyankha popanda jakisoni wa mankhwala kumapereka muyeso wa phindu lolimbitsa la chilimbikitsocho. Ndondomeko yachiwiri yolimbitsa thupi ingagwiritsidwenso ntchito ngati muyeso wa mphamvu zolimbitsa thupi za mankhwala [ 22 ]. Ntchito ya anyani ndi makoswe ikusonyeza kuti kuyankha kodalirika kwa cocaine kungakhazikitsidwe ndi ndondomeko yachiwiri [ 79 ]. Kupereka mankhwala osakhazikika kapena zinthu zomwe sizinali zokhazikika zomwe zimagwirizana ndi kupereka mankhwala zingayambitsenso kufunafuna mankhwala pambuyo pa kutha (kubwezeretsedwa). Mankhwala kapena zizindikiro zomwe zagwirizanitsidwa ndi kudzipatsa mankhwala kapena kulosera kudzipatsa mankhwala zitha kukhala zinthu zosokoneza zikagwiritsidwa ntchito mosakhazikika pambuyo pa kutha ndipo zidzayambitsa kubwezeretsanso khalidwe lofunafuna mankhwala [ 13 , 82 , 88 ] . Njira yotsatirira malo yomwe ili ndi zinthu zomwe zili ...

Ma substrates a mitsempha ya mitsempha ya zotsatira zabwino zolimbitsa thupi za mankhwala osokoneza bongo, makamaka ma substrates a mitsempha yobwezeretsa, amaphatikizapo kuyambitsa njira za glutamatergic kuchokera ku frontal cortex kupita ku nucleus accumbens ndi kuchokera ku basolateral amygdala kupita ku central nucleus ya amygdala ndi nucleus accumbens (kuti muwone ndemanga, onani [ 17 , 30 , 83 ].

Kusiya kugwiritsa ntchito mankhwala osokoneza bongo kwawonedwa kuchipatala. Omwe kale anali kugwiritsa ntchito mankhwala osokoneza bongo nthawi zambiri amanena zizindikiro zofanana ndi kusiya kugwiritsa ntchito mankhwala osokoneza bongo akabwerera ku malo okhudzana ndi zomwe adakumana nazo ndi mankhwala osokoneza bongo [ 62 ]. Mu kafukufuku woyesera wa omwe kale anali kugwiritsa ntchito mankhwala osokoneza bongo a heroin omwe adagwiritsidwa ntchito pa methadone, jakisoni wa antagonist wa opioid adaphatikizidwa mobwerezabwereza ndi kamvekedwe ndi fungo la peppermint [ 63 ]. Kuwonetsedwa kwa kamvekedwe ndi fungo lokha kunawonetsa zotsatira za kusasangalala komanso zizindikiro zenizeni zakusiya kugwiritsa ntchito mankhwala osokoneza bongo. Zotsatira zofanana zawonedwa m'mitundu yonse ya aprimate ndi makoswe. Aprimate ndi makoswe omwe amaloledwa kudzipatsa okha ma opioid kudzera m'mitsempha maola 23-24 patsiku adatsutsidwa ndi antagonist wa opioid ndi chilimbikitso chomwe sichinalowererepo kale. Antagonist wa opioid adawonetsa kuwonjezeka kofanana ndi kuyankha kwa opioid. Pambuyo pobwerezabwereza, kuwonetsa kwa chilimbikitso chokha kunapangitsa kuti kuyankha kwa opioid kukhale koyenera, kofanana ndi komwe kunawonedwa ndi antagonist wa opioid yekha [ 23 , 31 ]. Zotsatira zoyipa zomwe zimayambitsidwa ndi mankhwala osokoneza bongo zaphunziridwa kokha pankhani ya mankhwala a opioid m'zitsanzo za nyama koma zimakhudza amygdala ya basolateral [ 80 ] komanso njira zina zolumikizirana zofanana ndi zomwe zimayambitsidwa ndi mankhwala osokoneza bongo. Komabe, gawo lamalingaliro lomwe limayambitsa kusiya kugwiritsa ntchito mankhwala osokoneza bongo lingayambitsenso kupsinjika kwa ubongo komwe kumakhudzidwa ndi mphamvu zoyipa zosiya kugwiritsa ntchito mankhwala osokoneza bongo komanso kudziletsa kwa nthawi yayitali. Zoonadi, "kukumbukira kwamalingaliro" kumeneku kungathandize kuti munthu akhale ndi vuto la allostatic lomwe lingapitirire kupitirira kusiya kwa nthawi yayitali.

Ma substrates a mitsempha yokumbukira zamaganizo afufuzidwa kwambiri ndipo amagwirizana ndi ena mwa ma substrates a mitsempha yolimbikitsa zabwino ndi zoyipa zomwe zimagwirizanitsidwa ndi mankhwala osokoneza bongo. Ma substrates a mitsempha yokumbukira zamaganizo amapanganso kufanana kosangalatsa kwa neuropharmacological ndi ma substrates a mitsempha omwe amagwirizanitsidwa ndi malingaliro oipa omwe amagwirizanitsidwa ndi kudziletsa pakudalira mankhwala osokoneza bongo. Zochitika zamaganizo nthawi zambiri zimagwirizanitsidwa ndi zokumbukira zokhalitsa komanso zowoneka bwino zomwe zafotokozedwanso kuti "zokumbukira za flashbulb" [ 11 ]. Gawo lofunika kwambiri la ubongo lomwe limathandizira kuphatikiza zokumbukira zamaganizo zotere ndi basolateral amygdala ndi kulumikizana kwa mahomoni opsinjika ndi machitidwe ena a neuromodulatory noradrenergic omwe ali mmenemo [ 55 , 56 ]. Mu mndandanda wa maphunziro okongola a McGaugh, Roosendal, ndi anzake, basolateral amygdala idawonetsedwa kuti ikuthandizira zotsatira zokumbukira za mahomoni opsinjika a adrenal, ndi gawo lofunikira pakuyambitsa noradrenergic. Dongosolo la basolateral limawongolera kuphatikiza mitundu yosiyanasiyana ya chidziwitso. Mu maphunziro a anthu, kuchuluka kwa kuyambitsa kwa amgydala ndi kudzutsidwa kwamaganizo kumagwirizana kwambiri ndi kukumbukira pambuyo pake [ 9 ]. Kuphatikiza apo, monga tafotokozera pamwambapa, amygdala ya basolateral ili ndi gawo lofunika kwambiri pakulimbikitsa kulimbitsa kwabwino ndi koipa komwe kumakhudzana ndi mankhwala osokoneza bongo.

Udindo wa njira za noradrenergic pakukulitsa kulimbitsa kukumbukira unakhazikitsidwa mu maphunziro angapo omwe adagwiritsa ntchito jakisoni wa noradrenergic agonists ndi antagonists mu basolateral amygdala. Norepinephrine kapena noradrenergic agonists omwe adalowetsedwa mwachindunji mu basolateral amygdala nthawi yomweyo atangophunzitsidwa adathandizira kukumbukira ntchito zolimbitsa thupi monga kupewa kupewa [ 18 ], kukonza mantha [ 49 ], ntchito yodziwira zinthu m'madzi [ 26 ], ndi ntchito yozindikira zinthu [ 74 ]. Jakisoni wa β-noradrenergic antagonists atangophunzitsidwa anali ndi zotsatira zosiyana ndi kusokoneza kulimbitsa kukumbukira ntchito zolimbitsa thupi [ 20 , 26 , 59 ]. Mahomoni a Adrenal adathandizanso kuphatikiza ntchito zolimbitsa thupi kudzera mu kuyanjana ndi njira za noradrenergic mu basolateral amygdala [ 75 ]. Makamaka mogwirizana ndi lingaliro lamakono, kuyambitsa CRF mu basolateral amygdala kudzera mu kuletsa mapuloteni omangira CRF kunapangitsa kuti noradrenergic-dependent memory consolidation igwirizane [ 76 ]. Zotsatirazi zikusonyeza kuti CRF ingakhale ndi gawo losankha pophatikiza zokumbukira zokhalitsa za zochitika zolimbikitsa maganizo [ 76 ].

Kuphatikizika kwa machitidwe opsinjika muubongo pamlingo wawiri wa amygdala kungapereke maziko ofunikira a chikhumbo chofuna mankhwala osokoneza bongo mwa anthu omwe amadalira. Amygdala ya basolateral ili ndi chiwonetsero chachikulu ku nucleus yapakati ya amygala. Kawirikawiri, mu mantha, njira zolumikizirana zakhala zikupezeka ku amygdala ya basolateral, ndipo kuwonetsa mantha kwakhala kukupezeka ku zotsatira za amygdala: nucleus yapakati ya amygdala. Chifukwa chake, kuyambika kwa CRF ndi machitidwe a norepinephrine mu nucleus yapakati ya amygdala ndi basolateral amygdala kungakhudze madera awiri osiyana omwe angaphatikizidwe kuti alimbikitse gawo lililonse: mkhalidwe woipa wamalingaliro wosiya mwadzidzidzi ndi kudziletsa kwakanthawi komanso kuphatikiza zokumbukira za zokumana nazo zolimbikitsa malingaliro ( Chithunzi 4 ). Mwachitsanzo, nucleus yapakati ya amygdala yalembedwa bwino kuti imachokera kumadera aubongo omwe amakhudzidwa ndi kufotokozera malingaliro, monga hypothalamus ndi tsinde laubongo. Mosiyana ndi zimenezi, amygdala ya basolateral imaganiziridwa kuti imagwirizanitsa kuphatikiza zokumbukira za zokumana nazo zolimbikitsa malingaliro kudzera mu nucleus accumbens, nucleus ya caudate, hippocampus, ndi entorhinal cortex [ 56 ]. Mu mantha, mitundu iwiri yopikisana yokonza chidziwitso mkati mwa amygdala yaganiziridwa kuti imagwira ntchito panthawi yophunzira. Mu chitsanzo cha serial, chidziwitso chokhudza chilimbikitso chokhazikika ndi chilimbikitso chosakhazikika chimalowa ndikugwirizana ndi BLA, ndipo chidziwitsochi chimatumizidwa ku nucleus yapakati ya amygdala kuti chiwonetse mantha. Kapenanso, chitsanzo chofanana chikusonyeza kuti amygdala ya basolateral ndi nucleus yapakati ya amygdala zonse zimagwira ntchito zogwirizanitsa [ 98 ]. Chifukwa chake, machitidwe a mahomoni, noradrenergic, ndi CRF angaganizidwe kuti ayambitsidwa ndi zotsatira zoyipa za kusiya mankhwala kuti apange maziko a kulimbitsa koyipa komwe kumayendetsa kufunafuna mankhwala osokoneza bongo ndikuwonjezera njira zolumikizirana zomwe zimapititsa patsogolo mkhalidwe wamalingaliro womwe umathandizira kuyendetsa mkhalidwe wa allostatic wa chizolowezi.

Chithunzi chojambula mwachidule kufotokozera mgwirizanowu pakati pa kukhudzidwa ndi kukhudzidwa ndi kukumbukira maganizo. Mafotokozedwe aumtima amadziwika bwino kuti amachititsa kuti munthu ayambe kubwerera, ndipo njira yomwe ingakhale yofanana ndi yomwe imakhala yovuta kwambiri ...

Kuvomereza

Wolembayo angakonde kuthokoza Michael Arends kuti athandizidwe pokonzekera zolembedwazo. Kafukufuku anathandizidwa ndi a National Institute of Health amapereka AA06420 ndi AA08459 kuchokera ku National Institute on Alcohol Abuse and Alcohol, DA10072, DA04043, ndi DA04398 kuchokera ku National Institute on Abuse, ndi DK26741 kuchokera ku National Institute of Diabetes komanso Digestive and Kidney Diseases. Kafukufuku adathandizidwanso ndi Pearson Center for Alcoholism and Addiction Research. Ili ndilo buku la 19965 lochokera ku The Scripps Research Institute.

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