Nā Neuroimaging hōʻikeʻike o ka Frontoʻole i hoʻololiʻia - ka hana kīwī a me ke kūlana ma hope o ka hoʻopiʻiʻana i ka hoʻopiʻiʻana i ka Rat (2011)

Neuropsychopharmacology. 2011 Nov; 36 (12): 2431-2440.

Hoʻopukaʻia ma ka pūnaewele 2011 Jul 20. doi:  10.1038 / npp.2011.129

PMCID: PMC3194070

Ua pili kēiaʻatikala i kuhikuhiʻia e nā mea'ē aʻe ma ka PMC.

E hele:

Hōʻuluʻulu Manaʻo

Hoʻokahi pinepine ka lāʻau ketikona i ka mau hana hoʻokolohua ma kahi e aʻo ai nā rodents e hoʻokau pono iā lākou iho (SA) ka lāʻau. Eia nō naʻe, ʻaʻole maopopo ka nui o ka hoʻohālike ʻana o kēia mau hiʻohiʻona. Ua hoʻohana mākou i ka imaging résonance magnetic (MRI) e loiloi i ka hana basal a me ka hoʻokaʻawale ʻana i nā hana ʻōpala i nā kiʻekiʻu i kau ʻia ma kahi papa hana lōʻihi lōʻihi. Ma keʻano, ua ana mākou i ka nui o ke koko basebral (bCBV), kahi kikoʻī i hoʻokumu ʻia o ka metabolima basal, a me ka loiloi i ka ʻano o ka ʻōnaehana dopaminergic ma ke ʻano o ka hoʻomālamalama ʻana i ka pane o ka pharmacological MRI (phMRI) i hoʻoiho ʻia e ka dopamine-releaser amphetamine. Ua hōʻike ʻia nā kumuhana Cocaine i ka hōʻemi o ka bCBV i loko o nā wahi o fronto-cortical, nā nucleus accumbens, ventral hippocampus, a me thalamus. Ua hōʻike pū ʻia ka hui kokela i kahi pane hana i hoʻohui ʻia i ka amphetamine i loko o nā wahi ventrostriatal, kahi hopena e hoʻopulu nui ʻia ana me ka nui o ka kō o kokua. ʻO kahi pilina kū ʻole ma waena o ka bCBV i ka thalamus reticular a me ka pane o ka mua i hoʻopili ʻia e ka amphetamine i loaʻa i nā kumuhana hoʻomalu akā ʻaʻole i ka hui kokua, me ka hōʻike ʻana i ka interplay inhibitions i loko o kēia paikini attentional e hiki ke hoʻohuli ʻia e ka lāʻau lapaʻau. ʻO ka mea nui loa, ʻaʻole i hōʻike ka loiloi histopathological i nā loli nui o ka moe microvascular i loko o ka lolo o nā kumuwaiwai i hoʻomoʻa ʻia i ka popole, ke hōʻike nei i nā ʻike imaging ʻaʻole hiki ke hoʻopiʻi ʻia i ka pōʻino maʻi hoʻoneʻe kino. Kuhi kēia mau huaʻōlelo ʻo ia ka huaʻalā kākā, hōʻaia nui i ka cocaine SA i ka iole ka hopena o ka hoʻololi fonto fronto-cortical a striatal e hoʻolilo nei i ka hana neurobiological substrate no ka hōʻike o ke ʻano o ka hana paʻa ʻana i ka lāʻau lapaʻau.

Keywords: cocaine, fMRI, phMRI, dopamine, addiction, rat

Introduction

Hoʻohana ka cocaine cocaine i ka lōʻihi o ka hoʻololi ʻana o ka neurobiological i manaʻo ʻia e lilo i ka hoʻoheheʻe ʻana i ka mālama o ka mālama ʻana i ka lāʻau lapaʻau e wehewehe ana i ka hilinaʻi kokela.Koob ¶ AL, 1998). Ua hoʻomaka ka noiʻi neuroimaging kanaka i ke kukui i ke ʻano o kēia mau hoʻololi a me kā lākou pilina me nā ʻano kūpono a i ʻole nā ​​hōʻailona. ʻO ka hoʻoneʻe mua frontostriatal a me ka metabolism i loko o ka nui o ka lawehala kokoti i hōʻike ʻia e nā mea noiʻi he nui (ʻO Strickland ¶ AL, 1993; London ¶ AL, 1999; Volkow ¶ AL, 1992). Ua hoʻopili ʻia ka hana hūnā ʻia o nā palena o mua i ka neʻe ʻana o ka neʻe neʻeneʻo a me ka mana o ka hopu ʻana i ka lāʻau lapaʻau e hoʻōla pinepine ʻia ai (ʻO Strickland ¶ AL, 1993; Kalivas, 2004). ʻO ka hoʻopaʻa haʻawina Positron emitter (PET) me ka koho D2 hōʻike nā dopamine (DA) i nā kumuhana me nā haʻalulu kokahi e hōʻike mau nei i ka hōʻemi ʻana o D2 Loaʻa kahi ʻĀwili (Volkow ¶ AL, 1993; Martinez ¶ AL, 2004) a hoʻemi i ka pane dopaminergic i loko o ka nucleus accumbens a me nā mea ʻē aʻe o ka 'circuit reward' (Volkow ¶ AL, 1997), pili pū me ka hoʻohaʻahaʻa ʻana i nā hoʻoikaika kūlohelohe i ʻike ʻia ma kēia mau kumuhana (Volkow ¶ AL, 2007). Ua hōʻike ʻia nā noiʻi hou loa i ka hoʻololi ʻia o ka pilina pili o nā nū catecholamine i lalo o ka pale ʻana o ka hana cortical i ʻike ʻia ma nā lawehala cocaine, kahi ʻike e hōʻike ana i nā ala hou no nā hana neuroadaptational e pili ana i nā mokuʻāina addictive (Tomasi ¶ AL, 2010; Gu ¶ AL, 2010).

Hoʻolaha pinepine ʻia ka kuhi cocaine i ka paradigms hoʻokolohua ma kahi i hoʻomaʻamaʻa ʻia nāole i ka lāʻau lapaʻau ponoʻī (SA) i ka lāʻau lapaʻau. Ma ka hoʻohana ʻana i nā hiʻohiʻona SA ʻē aʻe, ua hiki i nā mea hoʻomaʻamaʻa ke hōʻulu hou i kekahi mau hiʻohiʻona nui o ka hoʻohui ʻana i ka lāʻau lapaʻau, e komo pū ana i ka ʻimi ʻimi puʻu.Vanderschuren a me Everitt, 2004), ke noi ʻana i nā lāʻau lapaʻau ʻole (ʻO Ahmed a me Koob, 1998), a hoʻonui i ke kumu holo i ka lāʻau lapaʻau (Paterson a me Markou, 2003). ʻO kēia mau hiʻohiʻona e hana i kēia mau hana hoʻokolohua a me ke ʻano maikaʻi o ka maka e nānā i nā hanana neuroplastic e pili pū ana me ka hoʻohana ʻana i ka lāʻau lapaʻau ʻoliʻoli (ʻO Roberts ¶ AL, 2007). Eia nō naʻe, pili i nā lāʻau lapaʻau e pili ana i ka addiction cocaine, e like me ka kuleana blunted DA i nā wahi striatal i ʻike ʻia ma nā haʻawina ʻo PET (Volkow ¶ AL, 1993; Martinez ¶ AL, 2004), mai hoʻohālikelike kūpono ʻia e nā kuʻuna pōkole pōkole, hiki i ka cocaine SA paradigms, kahi kahi e noʻonoʻo ʻia ai (ie, hoʻonui ʻia) pane ʻia nā dopaminergic (Narendran a me Martinez, 2008). Eia kekahi, ʻike ʻole ka nui o kēia mau hoʻohuli ʻana i ka loli o ka neurofunctional hoʻololi i ʻike ʻia i nā hana neuroimaging kanaka.

I ka noiʻi ʻana i kēia manawa, ua hoʻohana mākou i ka imaging magnet resonance imaging (MRI) e kiʻi i ka hana basal a ʻokaʻeu i ka hana o ka lolo i ka hoʻohālikelike i ka cocaine SA. Ua hana ʻia kahi protocol (lōʻihi 52), ka lōʻihi o ke komo (12 h) SA protocol e hōʻike i nā hiʻohiʻona o ka maʻi kiʻekiʻe, hoʻomāino paʻakai i loko o nā kānaka (Gawin me Ellinwood, 1988; Briand ¶ AL, 2008). Ua hoʻolōʻihi ʻia nā manawa abstinence e hōʻemi i ka hopena o ke aʻalapona o ka lāʻau lapaʻau a me ka hōʻoia i ka hoʻomau mau ʻia ʻana e hoʻokau i nā wai kiʻekiʻe o ka cocaine (ʻO Roberts ¶ AL, 2007). Ma hope o ka manawa detoxification a 10 lā, ua ana mākou i ka nui microbal basal cerebral blood volume (bCBV), kahi hōʻailona kuhikuhi o ka hoʻomaha hoʻomaha o ka lolo (Gaisler-Salomon ¶ AL, 2009; uuku ¶ AL, 2004), a loiloi i ka hopena o ka ʻōnaehana dopaminergic ma ke kaohi ʻana i ka pane hana i ʻāpono ʻia e ka DA-releaser amphetamine me ka hoʻohana ʻana i kahi protocolology Mactacac MRI (phMRI) kumu ʻikepili (ʻO Gozzi ¶ AL, 2010; ʻO Schwarz ¶ AL, 2004). Kuhi ʻia ka hoʻoponopono ʻana ma waena o ka hoʻomaha ʻana (bCBV) a me nā pane o ka amphetamine-evoked (rCBV) i kahi hoʻāʻo ʻana e ʻike i ka disregulation i loko o nā kahe i mālama ka hoʻokipa a me ka hana no ka hoʻopihapiha i nā ʻāpana ʻekahi. Hope, pou-mortem ua lawe ʻia nā hoʻokolohua histopathological e nānā i ka hiki o ka hopena o nā hopena vascular a me ka neurotoxic o ka cocaine SA lōʻihi i nā ʻike imaging.

NĀ MEI A ME NĀ MANAʻO

Ua hoʻokō ʻia nā hoʻokolohua kūpono ma muli o nā hoʻoponopono Līlani e alakaʻi ana i ka pono holoholona a me ka pale. Ua nānā ʻia nā protocols e ke komite mālama holoholona mālama kaiāulu, e like me nā kuhikuhi a nā kumu o nā kumu manuahi o Laboratory Animal Care (NIH publication 86 – 23, loiloi 1985).

Cocaine SA

Apana hana no ka cocaine SA

Ua hoʻāʻo ʻia ka loina i hoʻoiho ʻia i ka cocaine SA i loko o nā lumi hoʻokele e like me ka mea i hōʻike mua ʻia nei (Moretti ¶ AL, 2010). Ua hoʻokomo ʻia kēlā me kēia keʻena hoʻokolohua (Med Associates, St Albans, VT) me kahi kukui cue i kau ʻia ma luna o kēlā me kēia kīhāpai, a me ke ʻano leo 2900-Hz. Ua hoʻohui ʻia kahi pā infusion ma o ka catheter o waho i kahi wai kūwaho wai kū hoʻokahi (Instech Laboratories, Plymouth Meeting, PA). Kāohi ʻia ka ʻikepili a me nā ʻōnaehana hoʻonohonoho-hoʻonohonoho i nā polokalamu Med-PC (Med Associates).

Palapala lawainu SA

Ka nui o 30 kāne Lister-Hooded rats (Charles-River, Margate, Kent, UK) i kaupaona ʻia ʻo 275 – 300 g nā home i hoʻopaʻa ʻia i loko o kahi pākeke-a me ka keʻokeʻo-kahe makani i mālama ʻia me ka wai i loaʻa. ponoʻole. ^ E Ha yM. Ua kaupalena ʻia nā holoholona ma ka hoʻokolohua e mālama ai i ke koʻikoʻi kino o ke kino o 300 g (± 10 g).

Ma hope o ko lākou hōʻea ʻana, hoʻopihapiha ʻia nā kiʻi no ka wiki 1 a laila hoʻoiho ʻia i kahi catheter i loko o ka jugular vein e like me ka mea i hōʻike mua ʻia (Moretti ¶ AL, 2010). Ma hope o kahi lā hoʻōla 7-lā, lawe ʻia nāʻiole i ke keʻena hana. Hoʻomaka ʻia ka hana ʻo Cocaine SA ma lalo o ka lakio paʻa (FR) 1 ka papahana hoʻoikaika. Hoʻopili kēlā me kēia kaomi ma ka lever hana me kahi infusion 0.1 ml o kahi hopena cocaine hydrochloride (3 mg / ml, e like me 300 μg no ka hoʻokomo a me 1 mg / kg i nāʻiole e kaupaona ana 300 g) me ka mālamalama like o ka stimulus (cue ) ka mālam a me ka luku ʻia o ke kukui keʻena no 20 s. ʻO nā kaomi ma ka lever 'ʻeleu' ʻaʻohe hopena i hoʻolālā ʻia. Ua ukali ʻia kēlā me kēia infusion lāʻau ('delivery reward') e kahi retraction lever 20-s. Ua hoʻopau ʻia nā kau ʻekolu 'hoʻomaʻamaʻa' mua ma hope o 50 infusions a i ʻole 2 h mai ka hoʻomaka o ke kau. I nā kau he 30 e hiki mai ana, ua hoʻonui ʻia ka manawa komo cocaine i 12 h (1800-0600 h), ua hoʻemi ʻia ka mahele lāʻau i 0.150 μg / infusion (0.1 ml o 1.5 mg / ml solution kokaine, e like me 0.5 mg / kg i nāʻiole. ke kaupaona ʻana 300 g), a me FR hoʻonui iki i 3 (kau 4-6) a ma hope i 5 (koena 27 mau kau).

ʻO nā mea i nalowale catheter patency a i ʻole hele kino ʻole (ʻo ia hoʻi, ua hōʻike i nā hōʻailona o ka maʻi) i neʻe ʻia mai ka noiʻi (11 kumuhana holoʻokoʻa). Hōʻike pinepine ʻia ʻo 48 – 72 h abstinence i nā lā 16 (session 14, 72 h), 23 (session 18, 72 h), a me 31 (session 23, 48 h) e hōʻemi i ka hopena o ka maʻa cocaine-induced intoxication. Ua ukali ʻia ka maʻi 30 e kahi lōʻihi (5 mau lā) binge abstinence i ukali ʻia i ʻelua mau manawa hou. Ua hoʻokomo ʻia nā ʻano like ʻole ma muli o ka pono o ka hoʻonohonoho ʻana i ka manawa MRI scan a me ka protocol SA ma luna o ka helu nui o nā kumuhana e hana ana. ʻO kahi manawa detoxification ʻo 10-lā i loko o ka hale home i hoʻokomo ʻia ma mua o ka hoʻokolohua imaging.

Ke kaʻina hana no SA

Ua hoʻohana ʻia kahi pūʻulu o nā makika 14 i kahi kikowaena papa kuhikuhi. Ua hoʻokomo ʻia nā kumuhana me kahi catularter jugular a ua hoʻomau ʻia ma ke ʻano aʻoaʻo a me nā kaʻina SA (me ka helu, ka lōʻihi o nā papa SA, a me ka pau ʻole) e like me ka mea i hōʻike ʻia ma luna nei, koe wale nō ka hoʻohana ʻana o ka kaʻa (saline, 0.1 ml) ma kahi o ka cocaine i ka wā o ka mea hana. nā hana.

Hoʻomākaukau Hoʻonā Hoʻohanohano

Hoʻomākaukau holoholona

Ua hana ʻia nā haʻawina loina 10 ma hope o ka hālāwai SA hope i hala. Ua hōʻike mua ʻia ka nui o ka hoʻomākaukau ʻana o ka holoholona a me nā ʻāpana MRI i kahi kikoʻī.ʻO Gozzi ¶ AL, 2010; ʻO Schwarz ¶ AL, 2004).). ʻO ka pōkole, ua loiloi ʻia nā lālani me 3% halothane, tracheotomized, a me ka nui o ka ʻenekini. ʻO ka wahī a me ka vein femoral a ke kālai ʻia nā holoholona a me D-tubocurarine. Ma hope o ka hōʻemi ʻana, ua hoʻonohonoho ʻia ka pae halothane i 0.8%. Mālama ʻia ke ʻano o ke kino o nā kumuhana āpau i loko o ka pae ʻana o ka physiological a me ke ʻano o ke kahe koko o ke kino (MABP) i kiaʻi mau ʻia e ka wahine femoral.

Loaʻa kiʻi kiʻi MR

Ua loaʻa nā manawa Anatomical a me fMRI ma kahi ʻōnaehana Bruker Avance 4.7 Tesla. Hoʻonohonoho ʻia nā holoholona i kahi kākoʻo paʻa i hana ʻia, a me kahi 'Rat Brain' curved quadrature two-loop loaʻa coil (Bruker, Ettlingen, Kelemānia) i kau ʻia ma luna o ka iwi poʻo holoholona a paʻa i ka mea paʻa holoholona. A laila hoʻopaʻa ka mea paʻa holoholona i kahi resonator manu manu 72 mm (Bruker) i hoʻohana ʻia no ka radiofrequency transmit wale nō. ʻO nā wili ʻelua nā mea maʻamau i hāʻawi ʻia e ka mea hana.

AT2-loaʻa i ka nui anatomical volume me ke ʻano he RARE (TR = 5461 ms, TEpau= 72 ms, RARE factor 8, FOV 40 mm, 256 × 256 matrix, 20 paleʻole 1 mm ʻoka) i ukali ʻia e ka loaʻa ʻana o kahi manawa-wa (TRpau= 2700 ms, TEpau= 111 ms, RARE factor 32, dt = 27) me ka kiko o ka lapalapa, e hoʻopuka ana i kahi kiko pixel nui o ≈1 mm3. ^ E Ha yM. Ka huina piha o ka mana MRI manawa-XMUMX (58 repetitions) no nā hui ʻelua.

Ma hope o ʻelima mau kiʻi kiʻi, ua 2.67 ml / kg o ka mea hoʻonaninani ʻo Endorem (Guerbet, Roissy CdG Cedex, Palani) i ʻōlelo ʻia no ke hoʻololi ʻana i ka hōʻailona fMRI ma ka pale ʻana i ke koko koko cerebral (rCBV) (Mandeville ¶ AL, 1998; ʻO Schwarz ¶ AL, 2003).). Ua mālama ʻia ka D-amphetamine (0.5 mg / kg) ma ka hana liʻiliʻi ma 25 ma hope o ka hoʻohālikelike ʻana o ka agent, a ua loaʻa ka ʻikepili MRI ma luna o kahi manawa o 25 minia ma hope o ka paʻakikī. ʻO ke koho o -amphetamine i koho ʻia ma mua I loko o ka ola nā haʻawina (ʻO Schwarz ¶ AL, 2004; ʻO Gozzi ¶ AL, 2011). Mālama ka lāʻau i ka hoʻoikaika ʻana o ka lolo, ʻaʻole hana i nā pane 'kaupaku' rCBV (Micheli ¶ AL, 2007), a hoʻoiho aku i nā pane MABP transient e uku ʻia i ka home ma ke ʻano o ka halothane anesthesia (ʻO Gozzi ¶ AL, 2007; Zaharchuk ¶ AL, 1999).

KaʻIkepiliʻIkepili

ʻO Basal CBV

Hoʻopili ʻia ka ʻike kiʻi kiʻi kiʻi kiʻi mākaukau ʻo bCBV no kēlā me kēia hoʻokolohua i loko o ka kaʻe o ke kumu hoʻohālike laina.Worsley ¶ AL, 1992).). Ua hoʻohiolo ʻia nā kumuhana pilikino i kahi stereotaxic rat MRI template set (ʻO Schwarz ¶ AL, 2006A).). Ua hoʻololi ʻia nā hoʻololi koʻikoʻi i nā bCBV (t) ma ka kumu pixel-akamai e like me ka wā i hōʻike mua ʻia (Chen ¶ AL, 2001; Mandeville ¶ AL, 1998).). Ua helu ʻia nā manawa bCBV ma luna o kahi hāmeʻa 4.5-min manawa e hoʻomaka ana me 6.8 min ma hope o ka hopena o ka inikua. Hōʻailona nā bCBV no nā kumuhana pākēneka e ka hoʻomohala ʻana i ka manawa manawa ʻo 10. Ua kau ʻia ka laina lōkuhi hoʻopuka no ka moʻo ʻana i ka holoi holoi ʻokoʻa (ʻO Schwarz ¶ AL, 2003).). Ua lawe ʻia ka helu pākuhi ʻo Voxel-akamai me ka hoʻohana ʻana i FSL (Smith ¶ AL, 2004) ka hoʻohana ʻana i ka inea multilevel Bayesian, me 0.7 mm spatial smoothing, a Z paepae> 1.6, a me kahi paepae koʻikoʻi o ka ʻōpili i hoʻoponopono ʻia p= 0.01.

pane leo phMRI i D-amphetamine

Ua hoʻololi ʻia nā hoʻololi hāliʻi MRI i ka CBV fractional (rCBV) e like me ka mea i hōʻike mua ʻia (Mandeville ¶ AL, 1998) a hoʻopiʻi ʻia e hōʻike i kahi kūʻokoʻa kūʻokoʻa mai ke kahe koko (ʻO Schwarz ¶ AL, 2003).). Hoʻokuʻu ʻia ka pauku manawa manawa rCBV no ka hoʻokūkū amphetamine i helu ʻia ma 12.5-min prechallenge a me ka puka aniani 24-min postchallenge. Ua lawe ʻia nā helu Voxel-akamai e hoʻohana ana i ka FEAT me ka 0.7 mm spatial smoothing a me ka hoʻohana ʻana i kahi hana hoʻohālikelike (Hoʻohui Kahi Uʻi S1) e hopu ana i ka ʻike pilikino o ka pane ʻana o ka RCBV amphetamine-induced (ʻO Schwarz ¶ AL, 2006b).). ʻO nā hoʻohālikelike hui kiʻekiʻe kiʻekiʻe i lawe ʻia ʻia me ka nānā ʻana o multilevel Bayesian a ua paepae ʻia ma ka Z> 1.6 me kahi paepae koʻikoʻi o ka cluster i hoʻoponopono ʻia o p= 0.01. I mea e hōʻike like ai i ka hypothesis o ka hoʻololi striatal hoʻololi i ka D-amphetamine i loko o nā mauʻu cocaine, ua hoʻāla ʻia ʻo 3D mask mask o kahi nui subortortical area (striatum, thalamus, hippocampus, hypothalamus the striatum, ventral pallidum, BNST, a me amygdala) kahi hoʻonohonoho hou kelepona o ka atlas utukole (ʻO Schwarz ¶ AL, 2006A) a hoʻohana i ka prethreshold rCBV manawa manawa ma mua o ke ʻano kiʻekiʻe FSL kiʻekiʻe kiʻekiʻe. Hoʻonui kēia kaʻina hana i ka mana helu o ka helu ʻana ma ka hōʻemi ʻana i ka helu o nā hoʻohālikelike he nui (Huettel ¶ AL, 2004).). E noiʻi i nā kikoʻī kūloko o ka hopena i kahi ʻano hoʻokaʻawale a hypotesa a hoʻokaʻawale i nā hoʻemi ʻana i ka nui o ka pane ʻana i ka amphetamine ma ke ʻano o ka lolo, ua hoʻohua ʻia ka hana like ʻana me nā kikoʻī data RCBV non-masked (Hoʻohui Kuhi S5). Ka nui o ka manaʻo (VOI) ka manaʻo o nā waiwai bCBV a me nā papa manawa no ka hoʻokūkū amphetamine i lawe ʻia e like me ka mea i hōʻike mua ʻia nei (ʻO Schwarz ¶ AL, 2006A; ʻO Gozzi ¶ AL, 2008). Ua helu ʻia nā ʻikepili helu ma mean bCBV me ka hoʻāʻo ʻana i hoʻokahi ANOVA hōʻike ma hope o ka hoʻāʻo ʻana a Fisher no nā hoʻohālikelike he nui.

Ka wehewehe hoʻoponopono

ʻO nā palapala o ka bCBV correlated a me D-amphetamine-induced rCBV pane ma waena o nā kumuhana i helu ʻia i loko o ka hoʻolālā GLM ma ka pae pūʻulu me ka kuhikuhi ʻana i ka bCBV i nā wahi wae e hoʻohana ana me FSL (ʻO Schwarz ¶ AL, 2007A, 2007b).). Ua koho ʻia kekahi helu o nā VOI e pili ana i nā hualoaʻa o nā palapala ma ka hui o ka intergroup bCBV (medial prefrontal, insular, orbitofrontal, somatosensory cortex, caudate putamen, nucleus accumbens, reticular thalamus, a posteroventral thalamus). No kēlā me kēia VOI, ua hoʻokomo ʻia ka hoʻomohala hoʻolālā i kahi regressor e hopu ana i ka pūʻulu e hōʻike ana i ka hōʻailona BCBV ma ka pae anatomical a me kekahi e pili ana i ka vector zero-mean veCtor ma waena o ka N nā kumuhana i ka hui mai ka hoʻonohonoho hoʻonohonoho koho i koho ʻia. O ka ZUa helu ʻia nā kiʻi me nā mea hoʻohālike e hopu ana i nā hopena maikaʻi a maikaʻi ʻole me ka pane kiʻi ʻana, a ua luhi ʻia me Z> 1.6 a me kahi paepae koʻikoʻi o ka cluster i hoʻoponopono ʻia o p= 0.01. Kuhi ʻia nā laina lohi o ka bCBV a me nā pane o ka RCBV i ka noʻonoʻo ʻana i ka bCBV a me ka pane ʻana o ka hopena RCBV i ka amphetamine ma waena o nā kumuhana pākahi, ʻo kēia ka mea i hōʻike ʻia ma ke ʻano he pane ma luna o ka minima 20 min (4-24 min postinjection).

Kauhauʻauhau

Ua hana ʻia ka loiloi mōʻauwai ma 10 koko kokahi a me 8 ka koho kaulima mua ʻana e like me ka mea i hōʻike mua ʻia (Barroso-Moguel ¶ AL, 2002).). Ma hope o ka hoʻokolohua MRI, mālama ʻia nā kaika ma lalo o ka puʻuwai hohonu (halothane 5%), a me ka hoʻōla a 15-min aortic perfusion o ka media fixative (10% buffered formalin) i hana ʻia, e hana ʻia e ka infusion 5-min. Ua hoʻoneʻe ʻia nā puʻuwai kūpono i mālama ʻia a mālama ʻia i ka hopena hoʻoponopono no ka 24-72 h. A laila ua hana ʻia ka trrain trrain ma ka hoʻohana ʻana i kahi matrix utukole (ASI Instruments) i hoʻolālā ʻia no nā kiʻi e kaupaona ana i 200-400 g. Nā huaʻehā o Tissue i hoʻopili ʻia, māhele ʻia i loko o nā ʻāpana aniani 5-μm-ipo, a paʻa ʻia me ka hui ʻana o ka hematoxylin-eosin a me ka Luxol Fast Blue (Scholtz, 1977).). ʻO ka wili a me nā wahi i hoʻopaʻa ʻia ʻo ka cortex cortex, caudate putamen, corpus callosum, hippocampus (C2), cerebellum (purkinje cells), a me nā substantia nigra. Hana ʻia ka hoʻokolohua e nā mea noiʻi manuahi ʻelua makapō manuahi.

Nā Hua

Kaoli Chaine SA

Ua hoʻopau nā pahuhopu āpau i nā hālāwai koina 33 cocaine SA ma kahi o 52 mau lā. Ua hoʻohana ka papa hana SA me kahi koina o ka cocaine i ka manawa holoʻokoʻa.Hōʻike 1).). ʻO ka awelika kumulative kumakai o SA cocaine ma ke kumuhana he 1138.4 ± 33.3 mg / rat. Hōʻike ʻia nā kaila ikaika a me ka ʻaina kokua i mea holoʻokoʻa i ka wā o ka hoʻokolohua, ʻoiai ʻo ke kaila linear i hōʻike ʻia kahi nāwaliwali a koʻikoʻi (p<0.03, F = 4.62) kū i ka hoʻonui ʻana o ka lawe ʻana i ka cocaine ma mua o ka manawa ke hoʻohālikelike ʻia nā kau like like (kau 4-31, FR 3-5, lawena abstinence binge 48-72 h) (Kaha Helu S2).

Hōʻike 1 

(a) Ka helu o nā pēkē kaha ikaika i hoʻopaʻa ʻia i ka hui kokoleka SA (N= 19) a kāohi (saline SA, N= 14) i loko o nā papa SA. Ua hoʻomaka ʻia ke kaʻina hana ma Cocaine SA ma lalo o kahi pānaʻi paʻa (FR) 1 o ka hoʻoikaika. ʻO nā papa ʻenehana mua loa ...

ʻO Basal CBV

Ma ke noiʻi ʻana i ka hopena o ka hoʻokō cocaine i ka hana basal utak, ʻike mākou i ka bCBV i ka cocaine SA a me ka kāohi ʻana i nā kumuhana a me nā ʻapoʻī i nā wahi e hōʻike ana i nā hōʻailona nui i waena o nā hui. Hōʻike ʻo Rats me ka cocaine SA i hōʻemi nui ʻia ka bCBV i kekahi mau wahi o ka lolo i hoʻohālikelike ʻia i nā kaole ʻōwili (Nā Hōkū 2 a A me3) .3).). Ka hopena i kaulana i ka medial-prefrontal, cingulate, orbitofrontal cortex, septum, ventral hippocampus, wahi nui o ka ulu ʻana o ka nucleus, a me nā pōpoki pīpī a me nā retalam thalamic area. ʻAʻohe ʻokoʻa o ka CBV āpau ma waena o nā hui i nānā ʻia (p= 0.23, Nā haumāna t-iūi). ʻAʻole i ʻike ʻia kahi koulou ma waena o ka bCBV a me ka piha o ka cocaine coca i nā VOI a pau.P> 0.16, nā VOI āpau).

Hōʻike 2 

Ka hoʻōho aila ʻana o nā wahi e hōʻike ana i ka hoʻohaʻahaʻa nui loa i ka bCBV i loko o nā kiʻina i mālama pinepine ʻia i kā ka cocaine (cocaine SA; N= 20) vs nā kumuhana hoʻomalu (kaʻa SA; N= 14; Z> 1.6, hoʻoponopono ʻōpae p= 0.001) i nā kiko kikoʻī ...
Hōʻike 3 

Nānā BCBV ma nā ʻelena 3D volume anatomical (VOI, ʻO Schwarz ¶ AL, 2006A) no ka cocaine SA (N= 20) a kāohi kumuhana (paʻakai SA; N= 14). AcbC, ka nui o ke kumu o ka nucleus accumbens; AcbSh, shell o ka nucleus accumbens; Amy, amygdala; Cg, puali cortex; ...

Hōʻaliʻoniʻo ia i D-Amphetamine

I mea e hōʻoia ai i ka hoʻoneʻeʻana o ka dopaminergic striatal, ua ʻikea ʻia ka cocaine SA a me nā kaila ʻōpio me ka nui o DA-releaser amphetamine, a me ka ʻike ʻana i nā loli nui i ka nui o nā pane rCBV i kālele ʻia e ka lāʻau lapaʻau i loiloi ʻia ma o nā helu voxel-naau. E kū like me nā haʻawina mua (ʻO Schwarz ¶ AL, 2004), amphetamine hana hoʻōla ikaika o ka subortical a me nā ʻāpana cortical i nā pūʻulu ʻelua o nā kumuhana (Koho Hoʻohālike S3). Hōʻike pinepine ʻo Rats i ka cocaine i hōʻike i ka pane ʻana i ka amphetamine i ka striatum i hoʻohālikelike ʻia me nā kaole ʻōwili (Hōʻike 4 a me ke Koho Hoʻohui S3). ʻIke ʻia nā hopena ma nā kiko o ka manawa RCBV un-detrended (Hoʻohui Piha S4). I loko o nā kīkī i lawelawe ʻia ai i ka cocaine i mālama ʻia i ka nui o ka pane striatal i ka amphetamine i ʻike ʻia e inversely correlated me ka kumulamu kokola kumulamu (p= 0.03, Hōʻike 4).). Ua nānā ʻia nā kiko o ka hoʻoneʻe ʻana o ka pane hana kūpono i ka amphetamine i sensory-motor a me ka orbitofrontal cortex (Nā Koho Hoʻohui S3 a me S5).

Hōʻike 4 

ʻO ka nānā ʻana Orthogonal (a: uha, b: coronal, c: sagittal) o nā ʻekala ʻekepika subortical e hōʻike ana i ka pane o ka RCBV e pili ana i ka D-amphetamine i nā kiʻina i hana pinepine iā ia iho ʻo kā cocaine (cocaine SA; N= 20) vs nā kumuhana hoʻomalu (kaʻa SA; N= 14; ...

Hoʻolālā ʻana i ka hoʻonui ʻana o ka amphetamine i hoʻonui ʻia i MABP (Ke Koho Koho S6). ʻAʻole i hoʻopili iki ka hopena me ka pane ʻana i ka hana, a maikaʻi hoʻi i loko o ke kahe autoregulatory koko ma loko o nā pane ʻana o vasopressive i uku homeostatically me ka ʻole o ka hoʻopuka ʻana i nā loli nui rCBV (ʻO Gozzi ¶ AL, 2007; Zaharchuk ¶ AL, 1999).). ʻO nā kahe koko arterial (paCO2 a paO2) i ana i ka mua a ma hope o ka manawa manawa fMRI (Koho Hoʻohui S1). ʻAʻohe mea ʻokoʻa lahilahi i ka ʻāmua mua a i ʻole post-acquisition paCO2 loaʻa nā waiwai ma waena o nā hui (p> 0.1, nā hui āpau; hoʻokahi ala ANOVA).

Ka Hoʻohui ma waena o ka hana Basal a me ka hana hewa

I ka hoʻāʻo ʻana e hoʻokumu i kahi correlation ma waena o ka hana basal a evased functionally a me ka noiʻi ʻana i nā dysregulations i ka hoʻokele ʻana o kēia mau moku ʻelua, ua uʻi mākou i ka pilina ma waena o ka bCBV a me ka pane o ka amphetamine-indicated ma ke kāohi a me nā holoholona e mālama pono i kā cocaine. ʻAʻole i loaʻa ka hopena ma waena o nā bCBV a me nā pane o ka rCBV amphetamine-induced i loaʻa i nā hui i kekahi o nā wahi i hoʻokolokolo ʻia, me ka ʻike ʻole ʻia o ka thalamus a reticular a posterior-ventral i hōʻike ʻia, i nā kumuhana paʻa, kahi pilina inikua me rCBV amphetamine-induced ma fronto -nā ʻāpana āpau (ʻAmelika Hoʻohui S7 a me S8). ʻAʻole nō kēlā me kēia haʻaheo i hana ʻia ma ka pūʻulu kokina (Supplement Figure S8).

Kauhauʻauhau

ʻO ka loiloi histopathological o ka umauma keʻokeʻo a me ka hina hina, nā wahi a me ka interstitial compartment, a me ka macro- a me micro-vascular, ependymal, a me ka hana meningeal ʻaʻole i hōʻike i kekahi mau neurocellular, interstitial, a i ʻole nā ​​microvascular i nā hui pū kekahi. Ua hōʻike iki ʻole ʻia nā hōʻailona o ka pyknosis cellular a atrophy paha, hoʻololi ʻia ka leo, necrosis, a me interstitial edema i ʻike ʻia i kekahi o nā wahi o ka lolo e nānā ʻia, a me ka hoʻololi ʻia ʻana o ka moe microvascular a me ka capillary (ʻo ia hoʻi, ka basal membrane dilation a i ʻole rupture, hemorrhage, endothelial thickening a i ʻole wall fibrosis, thrombi or occlusions, and necrosis or vacuolation of endothelial cells).

KA HOOHOLO

ʻO nā palapala noi i kēia manawa ua loaʻa i ka cocaine paʻa mau ka nui o ka SA i ka iʻa ka hopena o ka loli neuroimaging e hoʻopili pili ana i nā ʻike kiʻi i loko o nā mea pili i kā cocaine. Kūʻai kūikawā, ua nānā mākou i ka hōʻemi o ka bCBV, kahi māka o ka hoʻomaha ʻana i ka hana noʻonoʻo, i nā wahi i loaʻa ke kōkua nui i nā hana cognitive kiʻekiʻe a me nā pale o nā neʻe (fronto-cortical areas), nānā a me ka manaʻo (fronto-hippocampal faritra), a me ka uku (mesolimbic wahi). Eia kekahi, pili ka cocaine SA i ka hoʻemi ʻana i ka striatal réactivity i ka hoʻoulu dopaminergic, a me ka hiki ʻana o nā hoʻololi pēpili putative i loko o ka pale o interplay ma waena o thalamus reticular a me ka hoʻōla ʻana o nā wahi fronto-cortical. Hāʻawi i kā mākou mau hopena neuroimaging e pili ana i ka nui o ka hoʻololi ʻana i ka hana o ka ʻoiole ma hope o ka ulu ʻana o ka kokela a me ka voluntary intake e hana ai i ka papa neʻe neʻe no ka hoʻohālikelike ʻana.

Hoʻomaʻamaʻa pinepine ʻia ka lāʻau kokoleka ma ka hanana paradigms kahi e aʻo ʻia ai nā rodents e hoʻokau i ka lawelawe ʻana i ka lāʻau lapaʻau. Maanei, ua hoʻokomo mākou i kahi protocol o ka cocaine SA wā lōʻihi a lōʻihi me ka manawa pīpī.Parsons ¶ AL, 1995; Wilson ¶ AL, 1994; ʻO Wilson lāua ʻo Kish, 1996) e kāohi i nā hiʻohiʻona o ka maʻi kiʻekiʻe, hōʻeha kino i ka loko o ke kanaka. Ua hōʻike ʻia nā paradigms SA lōʻihi i ka hana hou i nā hiʻohiʻona lapaʻau o nā ʻano hana kokoti me ka hoʻohana pū ʻana i ka lāʻau kūlohelohe ʻoiai ma ke ʻano o nā pilikia kūlohelohe.Vanderschuren a me Everitt, 2004), a kiʻekiʻe hoihoi e hoʻihoʻi i ka lāʻau lapaʻau ʻimi ʻona (ʻO Deroche-Gamonet ¶ AL, 2004).). Ka hana ʻole o ka protocol kūkaʻa (e uhi ana i ka ≈10% o ka lōʻihi o ka pālemakule o ka iole, Sharp a me La Regina, 1998) ʻae ʻia e hoʻohālikelike i nā heluna hoʻomanawanui me kahi mōʻaukala koʻikoʻi (> 6 mau mahina) o ka hōʻona ʻana o ka cocaine e like me nā mea i kākau inoa ʻia i nā noi neuroimaging kanaka, no laila ke hoʻonui nei i ka pili unuhi o kā mākou ʻike. Eia kekahi, ʻo ka hoʻohana ʻana o ke komo ākea ʻana i ka cocaine (ʻo ia hoʻi, h6 h) ʻike ʻia e hoʻohālikelike i nā hiʻohiʻona neurobeh behavioral kikoʻī o ka hoʻōla, e like me ka hoʻololi mau ʻana i nā hana noʻonoʻo (Briand ¶ AL, 2008; George ¶ AL, 2007), hoʻonui pana kumu no ka cocaine (Paterson a me Markou, 2003), a me ka neʻe i loko o ka hoʻohana i ka lāʻau (ʻO Ahmed a me Koob, 1998).). Ua hoʻolōʻihi ʻia nā manawa hana hoʻihoʻi i ka hōʻemi ʻana i ka hopena o ka hopena o ka lāʻau lapaʻau a me ka hōʻoia i ka hoʻomau mau ʻana i ka lawelawe ʻana i nā mana kiʻekiʻe o ka cocaine (ʻO Roberts ¶ AL, 2007).). ʻOiai ke kiʻekiʻe o ka kōnao kokoti i loaʻa me ka protocol o kēia manawa ua ʻoi aku ke kiʻekiʻe ma mua o ka mea e ʻike ʻia me ka loaʻa ʻole o nā paradigms pōkole.ʻAntslelo ¶ AL, 2004; Wee ¶ AL, 2007), e wehewehe ana i ka hemahema o ka lethality i nānā ʻia ma kēia noiʻi ʻana.

Hoʻohālikelike ʻia me nā protocols hoʻohana ʻole i ka mana, kahi i hōʻike ʻia ai ka hoʻohana ʻana i nā lāʻau lapaʻau ka nui a me ka haʻahaʻa o nā infusion i nā lā loli.Wilson ¶ AL, 1994), ke hoʻomohala nui o ka protocol e hoʻohana ʻia ma ʻaneʻi i hāpai ʻia ʻo SA o nā ʻano kiʻekiʻe o ka kokela. Kūlike ʻole i nā mea i hōʻike ʻia e nā hui ʻē aʻe (ʻO Ahmed a me Koob, 1998; Ferrario ¶ AL, 2005; Wee ¶ AL, 2007), ʻaʻole mākou i ʻike i nā hōʻike hōʻike kūlike o ka nui o ka pākōneka, ʻoiai naʻe he ʻano ka nui o ka komo ʻana i ka cocaine intake ma luna o nā hui i he mau lā.

ʻO kahi palena o ke k modelkohu e hana nei ʻaʻole ia i hoʻopili i nā ana o ka hoʻohana ʻana i ka lāʻau i loko o nā hopena maikaʻi ʻole (e like me, 'kūʻē i ka hoʻopaʻi' ʻO Deroche-Gamonet ¶ AL, 2004), he ʻano hana pono ʻia i manaʻo ʻia he koʻikoʻi diagnostic koʻikoʻi o ka hoʻohui ʻana i ke kanaka (AhahuiʻApelika Psychiatric Association, 2008).). No ka mea aia kēia hiʻohiʻona i ka ca. 20% o nā mea nui i ʻike ʻia i ka cocaine (ʻO Deroche-Gamonet ¶ AL, 2004; Ahmed, 2010), ke hoʻololi ʻia ka mea i hoʻololi ʻia ma ka hana i kēia manawa i ka hāʻawi ʻana mai nā kumuhana o nā kumuhana e hōʻike nei i kēia ʻano. Eia nō naʻe, eia ka hana a kēia mau hiʻohiʻona i nā hoʻololi maʻalahi i hoʻokaʻawale ʻia mai nā mea i manaʻo ʻia i kēia aʻo.

Ua kau ʻia kahi manawa holoi holoi 10 ma mua o ke aʻo ʻana i ka imaging aʻoi aku ka hopena o ka hopena o ka cocaine hopena a hoʻēmi ʻia i ka hopena o ke aʻole o ka pale ʻana i ka hopena o ka hana o ka lolo. ʻO ka hapa nui o ka hoʻololi ʻana o ka neurochemical a me ka hoʻonaninani e pili ana i ke kaila wili i loaʻa koke kahi hoʻomaka koke, ʻoki loa ma waena o 6 a me 72 h ma hope o ka pau ʻana o ka hoʻohana ʻana i nā lāʻau lapaʻau, a ʻoki ka hopena i loko o nā lā 2 – 7 mai ka lā i ka cocaine hope (Baumann lāua ʻo Rothman, 1998; ʻO Harris lāuaʻo Aston-Jones, 1993; Malin ¶ AL, 2000; ʻO Mutschler a me Miczek, 1998; Markou a me Koob, 1992).). A laila ʻaʻole hiki i nā loiloi imaging ke loaʻa ka perturbations nui mai nā hanana neilima e pili ana i ka hanana o ka cocaine kūloko. Ma ka ʻaoʻao ʻē aʻe, ʻike ʻia nā hoʻololi hana e ʻike ʻia mai nā hanana neuroadaptational lōʻihi (ʻo ia hoʻi, ka incubation o ka cocaine craving) i hōʻike ʻia e kūkulu nui ʻia ma hope o ka pau ʻana o ka kokua.Lu ¶ AL, 2004), a no ke ʻano o ka unuhi ʻana ma muli o ka hiki ke pili i ka propensity e hoʻohuli.

ʻAiʻi ʻo MRI o ka bCBV i ka hoʻokō ʻana i ka hakakā kiʻekiʻe i ka hoʻomaha ʻana i ka hana o ka lolo e hoʻopili paʻa ana me ka metabolism o ka ʻenekene a me nā kahe koko.Gaisler-Salomon ¶ AL, 2009; Kaukau ¶ AL, 2001; Gonzalez ¶ AL, 1995).). Hōʻike mākou i kā mākou ʻike i ka hōʻemi o ka bCBV hōʻemi i ka gyrus cingulated, cortex prefrontal, a orbitofrontal cortex, a me nā wahi striatal a me ka hippocampal mau kumuhana kokoleka SA. ʻO ka hopena frontostriatal i loko o ka ʻae like loa me ka noiʻi neuroimaging manuahi no ka hoʻohui ʻana i ka cocaine, kahi i mālama mau ʻia ai nā hana mua a me ka striatal.ʻO Strickland ¶ AL, 1993; Tumeh ¶ AL, 1990; London ¶ AL, 1999; Volkow ¶ AL, 1992, 1988) a ʻike ʻia e hui pū me ka hoʻopilikia cognitive, koi, a me ka nalowale o ka kaohi o ka pale ʻana i ka lawe ʻana i ka lāʻau lapaʻau e hiki ai i ka hoʻi hou aku (Goldstein ¶ AL, 2010; Kalivas ¶ AL, 2005; Kalivas, 2004; ʻO Hong ¶ AL, 2010; ʻO Strickland ¶ AL, 1993).). ʻO ka mea nui, nā nānā cognitive i nānā ma nā kiʻī i ʻae ʻia (ʻaʻole naʻe e kaupalena) ke komo ʻana i ka cocaine (Briand ¶ AL, 2008; George ¶ AL, 2007), he hanana e pili ana i ka hana hana a me nā hana nānā mau loa (ʻelua mau prefrontal cortex-hilinaʻi) a me nā hana e ʻike ai i ka hana (kahi hana hippocampus-hilinaʻi). Ke komo nei ka komo ʻana i nā ʻōnaehana hippocampal e like me ka hana a kēia ʻenehana i ka hanana ʻana a me ka hoʻomanaʻo ʻana, ʻelua mau hana e hoʻololi ʻia e ka cocaine a manaʻoʻiʻo ia ke hana i ka cue-elicited craving (loiloi ʻia e ka ʻO Koob a me Volkow, 2010).). Pēlā nō, hoʻoneʻe ʻia ka bCBV i ka nucleus accumbens i ʻike ʻole ʻia, hāʻawi ʻia ka pilina paʻa ma waena o ka hana fronto-cortical a me ka hana ʻana ma ka ʻai ʻana o ka selolostostrany DA.Kalivas ¶ AL, 2005; Nā lāhui ¶ AL, 2007).). Ke hoʻomau nei me kēia, nā hōʻike e pili ana i ka hana like ʻana o ka pēpē PET e hōʻike i nā pae haʻahaʻa o ka endogenous DA i ka mākeke cocaine pili i nā hoʻohālikelike kumuhana (Martinez ¶ AL, 2009) a me ka noiʻi haʻahaʻa hōʻike i hoʻemi ʻia ka hoʻohana ʻana i ka glucose i loko o nā wahi striatal ma luna o ka hoʻohana ʻana i ka cocaine hoʻohana, kahi ʻano i ʻoi aku ka nui o nā kūkā kokela.ʻO Porrino ¶ AL, 2007).

Ua nānā ʻia nā hoʻōla ʻana o nā bCBV i nā lula thalamic a me ka raphe nuclei. ʻO ka ʻike mua e pili ana i nā noiʻi neuroimaging kanaka e hōʻike ana i ke hoʻololi ʻia ʻana o ka lawehupena GABAergic i loko o ka thalamus o ka mea hoʻomake kokoti (Volkow ¶ AL, 1998) a me nā mea e pili ana i ka electrophysiological hōʻike o kahi kūlana overinhibition o nā retalam thalamic wahi ma hope o ka mālama ʻana i ka cocaine (Urbano ¶ AL, 2009).). ʻO ka mea mahalo, ʻo ka serotonin e hana i kahi hana kūlike a ka GABAergic neurons i ka reticular thalamus (McCormick a me Wang, 1991), ʻo ka hana hōʻemi o kēia mau nuclei a nānā i nā wahi o ka raphe i hiki ke hoʻopili pinepine ʻia a me kekahi hapa o ka pōkole pauahi.

ʻAʻole i loaʻa ka ʻikekelua ma waena o nā kōnao kokua a me ka bCBV i loaʻa i kekahi o nā VOI i hōʻike ʻia. ʻO ka nele o ka pili ʻana e hiki ke hōʻike i ka ʻokoʻa a ka pilikino i ka hopena o ka lāʻau lapaʻau, a i ʻole ka pili ʻana i ka nui o ka cocaine hoʻokaʻina kūʻokoʻa i ʻoi aku i ka nui o ka mea i koi ʻia e hana nui ai nā loli bCBV.

I ka hoʻāʻo ʻana e ʻike i kahi koina fMRI o ka hoʻopau i ka dopaminergic striatal i hōʻemi ʻia i ʻike ʻia i nā haʻawina aʻo kanaka (Volkow ¶ AL, 1990, 1993; Martinez ¶ AL, 2004), ua kiʻi pū mākou i ka pane hana i loaʻa e ka DA-releaser amphetamine me ka hoʻohana ʻana i kahi protocol phMRI (ʻO Schwarz ¶ AL, 2004; ʻO Bifone lāua ʻo Gozzi, 2010).). Ua hāʻawi ʻia kekahi mau haʻawina phMRI e hōʻike pono i ka pane striatal hemodynamic i hana ʻia e ka amphetamine e hōʻike pono ana i nā hopena dopaminergic (loiloi ʻia i loko Knutson a me Gibbs, 2007).). No ka hoʻohālikelike, ua hōʻike ʻia ka amphetamine i elicit BOLD a i ʻole ka rCBV i ka nui o nā wahi ma mua o nā ʻunana nui i loko o ka nui o ke ahonui a me ka pili o synaptic DA.Dixon ¶ AL, 2005; ren ¶ AL, 2009; ʻO Choi ¶ AL, 2006; ʻO Schwarz ¶ AL, 2007b; Hōʻailona ¶ AL, 2007).). Eia hou, ke hoʻopau ʻia nā pane rCBV amphetamine i koi ʻia ma nā wahi i loaʻa i ka DA.Chen ¶ AL, 1997, 1999), kahi hopena e hiki ke hoʻihoʻi hou ma hope o ka hoʻouluulu ʻana a ʻōlohelohe paha ʻoi.ʻO Bjorklund ¶ AL, 2002; Chen ¶ AL, 1999).). No laila, ʻo ka huina o kēia mau ikepili e hōʻike ana i nā pane o ka RCBV amphetamine-induced rCBV hiki ke hoʻohana pono i kahi hoʻohana ʻana i hōʻailona ma ka striatal DA neurotransmission. I loko o kēia papa hana, ka loaʻa ʻana o ka pane striatal rCBV stenatal e pili ana i ka amphetamine i ka hui kokoleka SA kokoleka e pili ana i ka emi ʻana o ka hana o ka hana dopaminergic ventrostriatal e like me nā mea i ʻike ʻia ma nā noiʻi PET i nā kānaka (Narendran a me Martinez, 2008). Hāʻawi kēia ʻike i ka manawa mua i kahi neuroimaging preclinical kūpono o kekahi o nā hōʻike loiloi loa o ka hoʻowalewale cocaine, ka mea i manaʻo ʻia he kuleana nui i ka 'hypohedonia' a me ka amotivation i hōʻike ʻia e nā kumuhana lāʻau ʻona i ka wā o ka haʻalele ʻana.Volkow ¶ AL, 1997). Kuhi kēia hopena i kahi leka koʻikoʻi koʻikoʻi ma waena o nā hoʻololi neuroadaptational klinikal a preclinical i hoʻokomo ʻia e ka cocaine ma nā ʻōnaehana DA, kahi hiʻohiʻona i ʻike ʻole ʻia e hoʻohālikelike ʻia e nā kūpale kūpuna cocaine, kahi e ʻike ʻia ai 'sensitized' (ie, hoʻonui) nā pane dopaminergic. (loiloi ʻia e Narendran a me Martinez, 2008).). Pēlā i ʻike ʻia ai nā pane striatal like ʻole i ʻike ʻia ma nā haʻawina neuroimaging rodent e hoʻohana ana i nā protocol protocol pohole (5 lā).Febo ¶ AL, 2005; Reese ¶ AL, 2004; a ʻo Gozzi, nā hualoaʻa i paʻi ʻole ʻia), hōʻike kā mākou data e, no kēia ʻano hana hoʻohālike i loko o ka rodents, hiki ke lōʻihi a loaʻa ke kīhāpai o nā koka. ʻO ka mea nui, ʻaʻole i nānā ʻia nā leʻaleʻa mikroskopika i nā hōʻiliʻili o ka vascular, neurocellular, a me interstitial of brains i ʻike ʻia i ka cocaine. He mea koʻikoʻi kēia hopena, no ka mea e ʻae ʻia e hāʻawi i kahi kōkua o ke kaʻina hana cerebrovascular abnormal ma luna o nā hemodynamic kaʻina o ka hana o ka lolo i hana ʻia (ʻo ia hoʻi, bCBV a me rCBV).

ʻO ka loiloi hoʻoponopono i waena o ka hoʻomaha a me ka amphetamine-evoked (rCBV) pane i hōʻike i kahi pilina kūlohelohe ma waena o bCBV ma nā wahi retalam thalamic a me ka hoʻālaʻi ʻana i mua o ka amphetamine i kahi kumumanaʻo, akā ʻaʻole ma ka hui kokua. Ua hōʻike ʻia nā haʻawina mua i ka pale ʻana o ka hana thalamic reticular e hiki ai ke hoʻonui i ka fronto-cortical dopaminergic neurotransmission (Jones ¶ AL, 1988), ka loaʻa ʻana me ka hoʻohui me nā hana pili o kēia mau ʻāina (Paxinos, 2008) a me ke kiʻekiʻe GABAergic kahakaha o ka reticular thalamic nucleus (Paxinos, 2008).). E like me nā mea hoʻokūkū mua i ka nucleus reticular thalamic e pāʻani nei i kahi kao kūʻokoʻa no ka hoʻokūkū kūloko.Zikopoulos lāua ʻo Barbas, 2006), ke kau nei mākou i ka nalowale o ka pilina ma waena o ke basal a me ka hana evaded i ʻike ʻia ma ka hui cocaine SA e pili ana me ka ʻike nui ʻole i ʻike i nā kiʻī i ʻae ʻia ke komo pono o ka cocaine (Briand ¶ AL, 2008; George ¶ AL, 2007).). ʻO ke kuleana koʻikoʻi no ka hana hakilima thalamo-mua i ka cocaine addiction ke kākoʻo ʻia e nā haʻawina neuroimaging hou e hōʻike nei i ka hoʻololi ʻana o ka thalamo-cortical hoʻololi i loko o ka cocaine abusers i lalo o ka hoʻomaha.Gu ¶ AL, 2010) a ke hana nei i ka hana kognitive (Tomasi ¶ AL, 2007).). Eia nō naʻe, no ka mea, ʻaʻole e hōʻike ka mea loulou i ka correlation isalation kumu, ʻike ʻia ka noiʻi e hoʻokaʻawale i ke ʻano maoli o kēia ʻike.

I ka hōʻākāka, hāʻawi mākou i nā hōʻike hōʻike o ka hana hoʻololi kino i loko o nā kahe e hele mau ana i ka cocaine SA lōʻihi. Kūkākūkā me nā ʻike neuroimaging haukapila, nā holoholona hūʻike i hōʻike ʻia i ka hoʻowalewale i ka hana basal ute ma nā wahi fronto-cortical a thalamic, a me ka hoʻokō ʻana i nā kuleana striatal i ka paʻakikī me ka DA-releaser amphetamine, he hopena i hoʻopili nui ʻia me ka huina o ka cocaine intake. ʻO ka hana maʻamau o kēia mau ʻike me nā hana neuroimaging i nā mea maʻi hoʻoleʻa kokela i kākoʻo i ka hoʻohana ʻana i nā paradigms SA lōʻihi a lōʻihi i loaʻa i nā kiʻina e ʻike ai i nā neuroadaptations i lalo o ka hoʻohui cocaine.

mau hoomaikai ana

Mahalo nui mākou iā Valerio Crestan lāua ʻo Giuliano Turrini no kā lākou kākoʻo loea maikaʻi loa i nā ana phMRI, a ʻo Pamela Rodegher mai Histolab, Verona, Italia, no ka hoʻomākaukau mōʻaukala.

Notes

ʻO nā mea kākau a pau nā limahana o GlaxoSmithKline. Hōʻike nā mea kākau, koe wale nō no ka loaʻa kālā mai ko lākou limahana mua, ʻaʻohe kākoʻo kālā a uku kālā paha i loaʻa mai kekahi ʻona a i ʻole hui pilikino ma mua o 3 mau makahiki i hala no ka ʻimi loiloi a me ka lawelawe ʻoihana a ʻaʻohe kuleana kālā pilikino i hiki ke ʻike ʻia ka hoʻokūkū ʻana o ka hoʻopaʻapaʻa hoihoi ʻana.

Nāʻaoʻao hemahema

Ua pili pū ka ʻike hoʻohui hoʻohui i ka pepa ma ka pūnaewele Neuropsychopharmacology (http://www.nature.com/npp)

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