ʻO ka overexpression o DeltaFosB e pili ana me ka cocaine i kāohiʻia i kāohiʻia i ka hoʻopauʻiaʻana o kaʻai i loko o nā mice. (2009)

KANAKA PAPA

Behav Neurosci. 2009 Apr; 123 (2): 397-407.

Aloha Aloha CS, Steffen C, Nestler EJ, Grigson PS.

kahi

Ke Keʻena ʻOliau a me nā Pono ʻAmelika Hui Pū ʻIa, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. [pale ʻia ka leka uila]

Hōʻuluʻulu Manaʻo

Hoʻokomo ʻo Rodents i ka hoʻohana ʻana i ka saccharin i ka wā e hoʻolako ai me kahi lāʻau hōʻino kino (ʻO Goudie, Dickins, & Thornton, 1978; ʻO Risinger & Boyce, 2002).). Ma ka mooolelo a nā mea kākau, ʻike ʻia kēia ʻano, ka mea i manaʻo ʻia he hoʻohālikelike uku, ka manaʻo ʻia e hoʻokaʻawale ʻia e ka hoʻomaka ʻana o nā waiwai ʻoluʻolu o ka lāʻau lapaʻau.PS Grigson, 1997; PS Grigson & CS Freet, 2000).). ʻOiai he ʻike nui ka ʻike nui e pili ana i ka neural kumu o ka uku a me ka hoʻohui, ʻike ʻia ka overexpression o ΔFosB i pili me ka hoʻonui nui aʻe o ka hōʻilo ʻana i ka lāʻau lapaʻau. No ke hāʻawi ʻana i kēia, ua pono nā mea kākau e kākoʻo ka ʻāpono nui o ΔFosB i mea e kākoʻo nui ʻia ka nui o ka lāʻau i ka hoʻokaʻawale ʻana o kahi makana kūlohelohe. No ka hoʻokolohua o kēia hypothesis, NSE-tTA × TetOp-ΔFosB mice (Chen et al., 1998) me ka orFosB maʻamau a i ʻole ka pōkole i ka striatum i hāʻawi ʻia i kahi c sac sacin a laila hoʻopaʻa ʻia me ka paʻakai, 10 mg / kg cocaine, a i ʻole 20 mg / kg cocaine. Kūlike ʻole i ka wānana mua, overexpression o ΔFosB i hoʻopili ʻia me ka pepeke a cocaine-indenate i hoʻopaʻa ʻia ma ka ulu ʻana o ka saccharin. He hypothesized ʻo ke kiʻekiʻe o ΔFosB ʻaʻole wale ka hoʻonui ʻana i ka waiwai uku o ka lāʻau lapaʻau, akā ʻo ka waiwai uku o ka saccharin cue pū kekahi.

Keywords: uku hoʻohālikelike, uku kūlohelohe, nā makika transgenic, CTA, intake

ʻO ΔFosB kahi lālā o ka ʻohana Fos o ka mea trans trans factor i loaʻa i ka makaʻala nui ke hiki ke hoʻololi i kahi molekue hiki ke mālama ʻia e pili ana i ka hana loiloi lōʻihi.McClung et al., 2004; ʻO Nestler, Barrot, a me ʻoe iho, 2001; ʻO Nestler, Kelz, & Chen, 1999).). ΔFosB hiki i ka homeJorissen et al., 2007) a heterodimerize me JunD (a i ka liʻiliʻi, JunB; Hiroi et al., 1998; Perez-Otano, Mandelzys, & Morgan, 1998) e hana i nā mea paʻakikī protein-1 (Chen et al., 1995; ʻO Curran & Franza, 1988; Nestler et al., 2001).). ʻO ka protein activator-1, a laila, paʻa i ka kahua hoʻohuihui protein-1 (TGAC / GTCA) e hoʻolaha ai a hoʻowalewale i ka hoʻoili ʻana o nā ʻano genes, akā, ʻaʻole i kaupalena ʻia, ka dinorphin, ka AMPA glutamate receptor subunit GluR2, cyclin-kinase 5 , a me nā kumu Kappa B (ʻO Chen, Kelz, Hope, Nakabeppu, & Nestler, 1997; Dobrazanski et al., 1991; Nakabeppu & Nathans, 1991; ʻO Yen, Wisdom, Tratner, & Verma, 1991).). I ka nucleus accumbens, ka piʻi ʻana o ka ΔFosB i pale i ka transkrip o ka dinorphin (McClung et al., 2004, aka ike Andersson, Westin, & Cenci, 2003) akā ke hoʻolaha nei i ka palapala o GluR2 (Kelz & Nestler, 2000), hoʻopio i ka kinase 5 (ʻO McClung & Nestler, 2003), a i nā 'aukaea kappa B (Ang et al., 2001).). Loaʻa ke hoʻohana ʻana i nā maʻi he nui o kēia mau ʻano (a me / a me kā lākou mau huahana) i mea e hoʻokaumaha ai i ka ʻike naʻau i ka lāʻau hōʻino. No ka laʻana, ʻo ka overexpression o GluR2 e hoʻohana ana i ka hoʻololi ʻana i ka ʻōnaehana viral i waena o nā lālani, a i ʻole blockade of dynorphin e ka agon-receptor antagonist nor-BNI i nā kiole, hoʻonui i nā hopena hopena o ka cocaine a me ka morphine, ia manawa (Kelz et al., 1999; Zachariou et al., 2006).

Hiki i kekahi mau mea ke hoʻonui i ΔFosB i ka lolo, a hiki i ke kiʻekiʻe ke kiʻekiʻe. ʻO ke kaumaha koʻikoʻi, nā lāʻau antipsychotic, a me nā lāʻau hōʻino e hoʻokiʻekiʻe i nā kiʻekiʻe ΔFosB i nā dorsal (caudate-putamen) a me ka ventral striatum (Atkins et al., 1999; Perrotti et al., 2004, 2008).). I loko o ka ventral striatum (ʻo ia hoʻi, accusensus nucleus), eia naʻe, kēlā me kēia ʻano o ka nui e hāpai i ka ΔFosB i nā ʻano kikoʻī. No ka mea lā, hoʻonanea ka kaumaha koʻikoʻi i ka ΔFosB i ka dinorphin + / sangkap P + a me enkephalin + mau ʻeke o nā neurons spiny dopamine i ka ventral striatum (Perrotti et al., 2004).). Hiki i nā lāʻau antipsychotic ke hoʻonui i ka ΔFosB i ka enkephalin + dopamine neurons i ka ventral striatum (Atkins et al., 1999; ʻO Hiroi & Graybiel, 1996), a me nā lāʻehā o ka hōʻino ʻana e hoʻokiʻekiʻe i ka ΔFosB i ka dinamphin + / waiwai P + dopamine neurons i ka ventral striatum (Moratalla, Elibol, Vallejo, & Graybiel, 1996; Nye, Hope, Kelz, Iadarola, & Nestler, 1995; Perrotti et al., 2008).). ʻO kēia kēia ka hopena o ka hōʻike ΔFosB i ka striatum dorsal a ma ka dynorphin + / substace P + dopamine neurons ma ka nucleus accumbens e pili ana mākou i ka "striatal" expression i kēia ʻatikala (ke ʻole i hōʻike ʻia i ʻole). he kūpono loa i nā uku kūlohelohe, nā mea hōʻino o ka hōʻino, a me ka hoʻohui hana (ʻO Colby, Whisler, Steffen, Nestler, a me ʻoe iho, 2003; McClung et al., 2004; Olausson et al., 2006; Werme et al., 2002), a ʻo ia ke kumu o ka hōʻike i loaʻa i nā kiʻina transgenic i hoʻohana ʻia i kā mākou mau haʻawina (Kelz et al., 1999).

ʻO ka mahalo, ʻo ka piʻi ʻana o ΔFosB e nā lāʻau hōʻino he pono ai i ka maʻi kūlohelohe ma mua o ka hoʻokūkū koʻikoʻi.McClung et al., 2004; Nye a me., 1995; ʻO Nye & Nestler, 1996). No laila, ʻoiai ka ʻike pinepine ʻana i ka lāʻau lapaʻau e hoʻonui nui i nā ʻōmole ʻohana Fos i ka striatum, e like me c-Fos a me FosB (ʻO Daunais & McGinty, 1994; B. Hope, Kosofsky, Hyman, & Nestler, 1992; Persico, Schindler, O'Hara, Brannock, & Uhl, 1993; Sheng & Greenberg, 1990), aia kahi liʻiliʻi liʻiliʻi e ulu nei i ΔFosB (Nestler, 2001a; Nestler et al., 1999). Eia nō naʻe, hoʻokahi mau mea, he kūpaʻa ʻo isFosB a loaʻa ka vivo half-life ma mua o 1 wiki e hoʻohālikelike ʻia me 10-12 hr no nā protein Fos ʻē aʻe (Chen et al., 1997). Hāʻawi kēia kūʻokoʻa i ka hōʻemi lohi o ΔFosB me ka hōʻike paʻa i ka lāʻau. ʻO nā ʻōmole Fos āpau, i ka hoʻohālikelike, hōʻike i kahi pane desensitized ma o ka manawa (Hope a me., 1992, 1994; Moratalla et al., 1996; Nye a me., 1995). ʻO ka hoʻolaha ʻana i nā lāʻau lapaʻau, a laila, e ʻae i ka ΔFosB e hōʻea i nā pae i hiki ai ke kau i ka hōʻike gen a lilo i kūpono.

Aia kahi kino ulu o ka puke nūpepa e hōʻike nei i ke kiʻekiʻe o ka ΔFosB e hoʻonui i ka ʻike i uku pono ʻia o nā lāʻau hōʻino. No ka laʻana, ʻoi aku ka makemake no nā wahi pili i nā lāʻau lapaʻau, i hoʻohālikelike ʻia e ka wahi kūpono i ke ʻano, ua hoʻonui ʻia i nā kiʻi me ka hoʻokiʻekiʻe atedFosB ma ka striatum (Kelz et al., 1999). Loaʻa ka loaʻa ʻana a me ka mālama pono ʻana i nā hana lawe i ka lāʻau, me ka hoʻowalewale ʻana i ka lāʻau lapaʻau, hoʻohālike ʻia me nā kiʻī me kahi kiʻekiʻe ΔFosB (Colby et al., 2003). ʻOiai ka holomua ʻana i ʻike i ka hopena o ka ΔFosB i nā nui o ka hoʻohui ʻana i ka lāʻau lapaʻau, hoʻokahi wahi i ʻike ʻole ʻia ai ka hopena o ΔFosB ma ka hoʻokaʻina o nā lāʻau lapaʻau i ka hoʻēmi ʻia ʻana o nā makana kūlohelohe. I ke kanaka, ua hōʻike ʻia kēia ʻano ma ka hoʻemi ʻana o ka hana no ka hana, nā hoaaloha, ʻohana a me nā waiwai kālā (me ka ʻike, Goldstein et al., 2006, 2008; Jones, Casswell, & Zhang, 1995; Nair et al., 1997; Santolaria-Fernandez et al., 1995).

Hōʻike ʻia kā mākou mau ʻike e hiki i ke kumu o ka hōʻino i ke kaila i ke kanaka ke hoʻohālikelike ʻia i loko o ka rodents e hoʻohana ana i ka paradigm uku hoʻohālikelike.ʻO Grigson & Twining, 2002). I loko o kēia paradigm, hiki ke komo i kahi cākare saccharin ʻē aʻe a ukali ʻia e ka loaʻa ʻana o kahi lāʻau lapaʻau, e like me ka morphine a i ʻole kokā. Ma lalo o kēia mau kūlana, hele mai nā kiʻī a me nā kiʻowela e pale aku i ka ʻai ʻana i ka cue keʻena ma ke kali ʻana o ka lawelawe o ka lāʻau lapaʻau (Grigson, 1997; ʻO Grigson & Twining, 2002; ʻO Risinger & Boyce, 2002). Wahi a ka hypothesis hoʻohālikelike uku, ʻo ka hoʻopili ʻana i ka cula uku kūlohelohe e pale ʻia ma hope o nā pakanā me ka lāʻau o ka hōʻino, ma ka mea mua (ʻike ʻia) Wheeler et al., 2008), no ka mea, ʻo ke kumukūʻai o ka palū puhaka gustatory i hoʻohālikelike ʻia i nā waiwai kūpono o ka lāʻau (Grigson, 1997). ʻOkoʻa ka nānā ʻana i ka moʻo o ka manaʻo hoʻāliu lōʻihi (CTA) o ka ʻikepili - ʻo ia hoʻi, ʻokoʻa ka ʻike mai nā manaʻo mai ka mea i ʻalo ʻia ka huina o ka ʻano cue no ka mea ua wānana ʻia nā waiwai ʻokoʻa o ke ʻano (a)Nachman, Lester, & Le Magnen, 1970; ʻO Riley & Tuck, 1985).

Inā kūpono ka hypothesis hoʻohālikelike, kekahi ʻano a i ʻole ke kūlana e hoʻonui ai i ka ʻike ʻike o ka uku lapaʻau e pono ai lākou e pale aku i ka liʻiliʻi o ka saccharin cue. Ma ke ʻano, ua hōʻike ka nui o ka maʻi i nā lālani Lewis i ka nui o ka ʻūʻā ʻana o ka pahu sacca ma hope o ka pahu waihui-cocaine ma mua o nā mea i ʻike ʻole ʻia i nā mea aloha momona Fischer (ʻO Grigson & Freet, 2000). ʻO ka ʻikena ʻo Sprague-Dawley hoʻi ke hōʻike aku nei i ka nui o ka ʻalo ʻana i ka cue ʻano i pānaʻi ʻia me ka cocaine a i ʻole ka sucrose ma hope o ka mōʻaukala o ka mālama ʻano morphine (ʻO Grigson, Wheeler, Wheeler, & Ballard, 2001). ʻO ka mea mahalo, ua mau nā lāʻau a me nā kahe a ʻo Sprague-Dawley me ka mōʻaukala o ka mālama hemphine i hāpai i ka ΔFosB i loko o ka accumbens nucleus (ʻO Haile, Hiroi, Nestler, & Kosten, 2001; ʻO Nye & Nestler, 1996). Hoʻomaka pololei ka hoʻokolohua 1 i ka hana o ΔFosB i ka hōʻeuʻeu ʻana i ka lāʻau lapaʻau i ka hoʻomakeke ʻia o ka hoʻoulu ʻana i ka maʻi (CS) ma ka loiloi ʻana i ka hoʻomakeʻa kokina i ka hoʻokomo ʻana i kahi cākī saccharin i nā kiʻina e hōʻeha i kēia kumu transwriter i ka striatum.

Hōʻike 1

Ua hōʻike ʻia nā noi ʻana i ka mua i nā kiʻina i ka ʻimi ʻana i ka pā hele e hoʻohālikelike ai i ka lāʻau hōʻino ma ke ʻano e like me ka mea i ʻike i nā kiʻi (ʻO Risinger & Boyce, 2002; Schroy, 2006). ʻO ka nui e like me nā haʻawina e pili ana i nā kiʻī, ua hoʻohana ʻia kēia mau noi i ka hoʻokaʻawale ʻana i ka wai a me kahi hoʻonā saccharin 0.15% makemake e like me ka CS (Bachmanov, Tordoff, & Beauchamp, 2001; ʻO Tordoff & Bachmanov, 2003). I loko o kēia mau hoʻokolohua, ua hōʻemi ʻia ka hoʻokomo ʻana i ka c sac sacin i ka wā e komo ai ka ʻeke i ka saccharin e ukali ʻia ma ka inikua o 10 mg / kg cocaine (i nā kunika DBA / 2) a i ʻole 20 mg / kg cocaine (i DBA / 2 a me C57BL / 6 mau kiʻo )ʻO Risinger & Boyce, 2002; Schroy, 2006). No laila, ua loiloi ʻo eksperiment 1 i ka ʻohi ʻana ʻana i ka cue sacrein 0.15% i ka wā e hui pū ai me ka paʻakai, 10 mg / kg cocaine, a i ʻole 20 mg / kg cocaine i ka wai-hoʻohemo i ka NSE-tTA × TetOp-ΔFosB Line A iole. ʻO kēia mau kiʻina transgenic pākeke (SJL × C57BL / 6 background) hōʻike i ka overplpression selectivepression o ΔFosB i ka striatum ma ka weheʻana o doxycycline mai ka wai (Chen et al., 1998). Ma ke kumu o ka ʻikepili i loaʻa i nā kiore, ua hoʻāʻo mākou i ka piʻi o ka ΔFosB i kēia mau kiole e hoʻonui ai i nā hopena hopena o ka lāʻau a pēlā hoʻi i hōʻemi ʻia ai ka pehu ʻana i ka hana ʻana i ka cue saccharin pili i ka mana ΔFosB maʻamau.

hana

Nā Kaupapa

ʻO nā kumuhana he 60 kāne NSE-tTA × TetOp-ΔFosB Line A i nā kiʻi bitransgenic. Ua hooulu ʻia nā kiole e ka holoholona holoholona ma ke Kulanui o Texas Southwestern Medical Center ma Dallas, Texas, a mālama ʻia ma 100 μg doxycycline / ml i ka wai inu. Mālama kēia ʻano i ke ʻano piha o ka hōʻike transgenic ΔFosB a laila e hiki ai i ka hoʻomohala maʻamau (e like me ka mea i hōʻike ʻia i loko Chen et al., 1998). A laila hali ʻia nā kiole i ka hale holoholona ma ke Kulanui o Kaʻāina ʻo Pennsylvania State University of Medicine ma Hershey, Pennsylvania, a hoʻokaʻawale ʻia ma nā mahina 2 (ua mālama ʻia nā kiʻi a pau ma doxycycline i ka wā o ka halihali a ma ka wā quantine) I ka hoʻokuʻu ʻana mai ka quantine, ka hapalua o nā ipo (n = 30) ua hana ʻia ka doxycycline, a ua ʻae ʻia ka overexpression ΔFosB e hoʻomaka no nā wiki ma 8 ma mua o ka hoʻāʻo ʻana, ʻo ka manawa e pono ai ka hana maxFosB maksimal (ʻO McClung & Nestler, 2003). ʻO ke koena o ka mauʻu (n = 30) i noho ma ka doxycycline no ka lōʻihi o ke aʻo ʻana. Wehepaʻa ʻia nā pōpoki ma waena o 31.2 g a me 45.0 g i ka hoʻomaka ʻana o ka hoʻokolohua a paʻa mau ʻia ma ke ʻano maʻamau, ʻike ʻia nā pāpaʻi palaka ma kahi ʻano mālama manu (21 ° C) me kahi mālama holoholona mālama ʻUmi a 12-hr-kukui i 7: 00 am). Ua hana ʻia nā hoʻokolohua āpau āpau ma 2 hr (9: 00 am) a me 7 hr (2: 00 pm) i loko o ka māmā o ka hopena. Mālama ʻia nā kiʻi me ka loaʻa ʻole o ka hulina ʻana i ka ʻai ʻo Harlan Teklad rodent diet (W) 8604 a me ka wai, koe wale nō kahi e haʻi ʻia.

i hoʻomākaukauʻia

ʻO ka hana hoʻokolohua āpau i mālama ʻia ma nā hale mālama home. Ua hoʻohana ʻia nā paileta weliweli Mohr i hoʻolako iā dH2ʻO ka huakaʻi a me ka saccharin. Ua hoʻohuli ʻia nā pipettes i nā kūloko aniani ma ka wehe ʻana i nā pihi kala. Kūkulu kahi mea kīwaha me ke kila kila i hoʻokomo ʻia ma loko o ka ʻaoʻao a laila waiho ʻia i lalo o ka cylinder, a me kahi pahu hana pīpī like (minus ka spout) i hoʻopaʻa ʻia ma luna o kahi cylinder. Inu o dH2ʻO O a me saccharin i hoʻopaʻa ʻia ma 1 / 10 ml.

Ke Kaʻina hana

Kaupaona ʻia nā kumuhana āpau i hoʻokahi lā ma ke ao. Ma hope o ka hoʻokuʻu ʻia mai o ka kuʻikepili, a e like me ka mea i hōʻike ʻia, ʻo ka mau kiole overexpression ΔFosB (n = 30) i lawe ʻia aku ma 100 μg / ml doxycycline. Ua loaʻa kēia mau kiʻio unadulterated dH2O ke koena o ka hoʻopaʻa ʻana, a ʻo ka hapa ʻē aʻe o nā ʻiole (n = 30), nā hui maʻamau ΔFosB, i hoʻomau ma ka doxycycline. Ma hope o nā hebedoma 8 o ka exFosB overexpression, ua loiloi ʻia ka hana kai. No nā ana ʻana i ka pae ʻāina, ua kau ʻia nā kiʻi a pau ma ka papaʻaina o ka wai e loaʻa ai ke komo ʻana i ka dH2O (me a ʻole ʻole doxycycline i kau ʻia i ka hui mālama lāʻau) no 1 hr hoʻomaka i 9: 00 am a no 2 hr hoʻomaka i 2: 00 pm Baseline intake a me ke kaumaha o ke kino i hoʻopaʻa ʻia no 1 pule. I ka hoʻāʻo ʻana, loaʻa i nā kiʻi a pau 1 hr hiki i ka 0.15% saccharin i ke kakahiaka i ukali koke ʻia e ka maʻi intraperitoneal saline (n = 10 / cell), 10 mg / kg cocaine (n = 10 / cell), a i ʻole 20 mg / kg cocaine (n = 10 / hale). Ua loaʻa nā lāʻau hoʻōla i ke kinipōpō "48 hr no ʻelima mau ho'āʻo. E hoʻokau i ka hydration, loaʻa i nā kumuhana āpau 2 hr holo i ka dH2ʻO ʻoe a i ʻole 100 /g / ml doxycycline i kēlā me kēia ahiahi a me 1 hr manawa e hele ai i dH2ʻO O a i ʻole 100 μg / ml doxycycline i kēlā me kēia kakahiaka ma waena o nā hoʻokolohua hoʻokolohua, e like me ka hōʻike ʻana ma ka pūʻulu. Ua loaʻa mai ʻo Saccharin mai ka ʻElma Chemical Company, ʻo St. Louis, MO, a me ka cocaine HCl i hoʻolako ʻia e ka National Institute on Drug Abuse. Hāʻawi ʻia ka hoʻonā kupa i ka mahana o ka lumi.

Nā hualoaʻa a me ka kūkā

Kikowaena CS

Kuhi ʻia ka intake a me ke kaumaha o ke kino me ka hoʻohana ʻana i ka 2 × 3 × 5 hui ʻikepili me ka wili o nā ʻano (ANOVA) e like me ka ʻano lāʻau (maʻamau ma overexpression o ΔFosB), ka lāʻau lapaʻau (saline, 10 mg / kg cocaine, a i ʻole 20 mg / kg cocaine), a me mau hoʻāʻo (1 – 5). Ua mālama ʻia nā hoʻokolohua post hoc, kahi kūpono, e hoʻohana ana i nā hoʻokele Neuman-Keuls me kahi alpha o .05. Ka nānā ʻana o Hōʻike 1 hōʻike ana i ka hoʻouka ʻana o ΔFosB i ka striatum i pili me ka hoʻēmi ʻana ma mua o ka hoʻonui ʻana o ka hoʻomake o ka cocaine-induced of intake o ka saccharin cue.

Hōʻike 1 

Ka waiwai (± SEM) intake (ml / 1 hr) o 0.15% saccharin ma hope o elima mau peke me ka intraperitoneal injection o saline, 10 mg / kg cocaine, a i ʻole 20 mg / kg cocaine ma NSE-tTA × TetOp-ΔFosB Line A mau kiʻina me maʻamau (panel hema) a hoʻokiʻekiʻe ʻia ...

Hāʻawi ʻia ke kākoʻo no kēia nānā ʻana i ka nānā ʻana o ka hoc analect o kahi ʻano nui ʻo ka maʻi × Drug × Trials interaction, F(8, 212) = 2.08, p <.04. ʻO ke kikoʻī, nā hopena o ka post hoc Newman – Keuls hōʻike hōʻike ʻia ʻoiai ʻo ka hopena o 10 mg / kg o ka cocaine ka mea maikaʻi ʻole i ka hoʻoliʻiliʻi CS i nā hui mālama ʻelua (p > .05), ʻoi aku ka maikaʻi o ka mahele lāʻau 20 mg / kg i nā ʻiole me ke kiʻekiʻe o ka ΔFosB (e nānā Hōʻike 1, hoʻonohonoho ʻākau). ʻO ia, ʻo ka hoʻōla me ka 20 mg / kg waiʻu o ka cocaine i hōʻemi nui i ka ʻai o ka saccharin cue pili i ka paʻakai pākahi o kēlā me kēia hui e mālama ʻia ana nā paʻakai ma nā Trials 2-5 (ps <.05), ʻo nāʻiole me ka hoʻokiʻekiʻe kiʻekiʻe o ka ΔFosB i hoʻopau nui ʻia o ka cake saccharin i hui pū ʻia me ka cocaine 20 mg / kg ma mua o nā mana hōʻike maʻamau. He mea nui kēia ʻano hana ma nā hoʻāʻo 3-5 ( ps <.05).

ʻO ke kaumaha o ke kino

ʻAʻole i ka lihilihi ʻana o ka ΔFosB i ka striatum a i ʻole ke kala ʻana i ka lāʻau lapaʻau i hoʻololi nui ʻia i ke kaumaha kino kino. Ua kākoʻo ʻia kēia hopena ʻana e nā hopena koʻikoʻi nonsignificant o ka mālama ʻana, F <1, a i ʻole lāʻau lāʻau, F(2, 53) = 1.07, p = .35. He mea nui ka hopena nui o nā hoʻokolohua, F(5, 265) = 10.54, p <.0001, e hōʻike ana ua loli ke kaumaha o ke kino ma luna o nā hoʻāʻo ʻana. ʻO ka mea hope loa, ʻoiai ʻo 2 × 3 × 6 mau hana hou i hōʻike ʻia ANOVA hōʻike i kahi ʻano nui Kālepa ʻana ʻo × Nā hoʻāʻo ʻana hoʻāʻo, F(10, 265) = 4.35, p <.01, ʻike ʻole nā ​​hopena o nā hoʻokolohua post hoc.

Hoʻomoe wai ka wai

Hoʻomaikaʻi ʻia ka uū o dH2O (ml / h) i nā lā ma waena o nā hōʻike hoʻokolohua (baseline, hōʻike ʻia nā hōʻike W1-W4) Hōʻike 2 (luna hema a me nā ʻaoʻao ʻākau).

Hōʻike 2 

Kaʻai (± SEM) intake o dH2E i ke kakahiaka (ml / 1 hr; nā papa ʻākau) a i ke ahiahi (ml / 2 hr; panels ma lalo) i NSE-tTA × TetOp-ΔFosB Line He mau kiʻina me nā hanana (mau ʻaoʻao hema) a i ʻole na kiʻekiʻe (ʻele panika) nā pae o ΔFosB i ka striatum ...

A 2 × 3 × 5 ka hānai ANANA ANOVA i hōʻike ʻia ʻaʻole i pau ka overexpression o ΔFosB i ka striatum a ʻaʻole i ʻike i nā lāʻau lapaʻau i hoʻololi nui ʻia i ke kakahiaka dH2O ka hoʻohana ʻana e like me ka hōʻike ʻana iā nonsignificant × Ka Hoʻomaka Hoʻāla HoloiF <1). Eia hou, ʻaʻole ka hopena nui o ka mālama ʻana. F <1, a i ʻole lāʻau lāʻau, F(2, 53) = 2.55, p = .09, ʻaʻohe maikaʻi o ka Hoʻōla lāʻau Hoʻōla lāʻau, F(8, 212) = 1.57, p = .14, ua waiwai nui ka helu.

Ka ʻauʻa wai ahiahi

Inu o dH2ʻO no ka manawa helu 2-hr manawa i ke ahiahi i hōʻike ʻia i nā hōʻike āpau Hōʻike 2 (nā ʻaoʻao hema a me nā ʻaoʻao hema). ʻAʻole koʻikoʻi ka hopena nui o ka mālama ʻana (F <1), e hōʻike nei ʻaʻole pili ka overexpression o ΔFosB i ke awakea dH2ʻO ka hohonu holoʻokoʻa. ʻO ka hopena nui o ka lāʻau lapaʻau, naʻe, ua loaʻa i ka helu statistic, F(2, 53) = 7.95, p <.001, e like me ka launa ʻana o nā lāʻau × × Nā hoʻāʻo e launa pū, F(18, 477) = 2.12, p <.005. Ua hōʻike ʻia nā hōʻike hoc o kēia ANOVA ʻekolu ala i kēlā awakea dH2ʻO ke komo i loko o nā hui kokela 10 mg / kg, ʻaʻole i like ʻole i ka hopena o ka paʻakai (ps> .05). Eia naʻe, awakea dH2I ka nui o ka hoʻohana ʻana i ka hui 20 mg / kg i hoʻohālikelike ʻia me ko lākou mau paʻakai, a ua nui kēia hopena i nā hoʻokolohua hakakā ma nā puʻupuʻu i pale aku ai i ka hoʻokomo ʻana i ka c sac sacin i ke kakahiaka (ʻo ia hoʻi, ʻo Trials 3, 4, a me 5 i nā kiole me ka normal ΔFosB a me nā hoʻāʻo 4 a me 5 i nā kiole me ka piʻi ΔFosB, ps <.05).

Hōʻike 2

ʻO nā hopena i loaʻa i loko o ka hōʻikeʻo 1 e kū'ē i ka mea i wānana ʻia ma ka kumu o nā kiʻi i paʻi ʻia ma mua. ʻO ka kiʻiwahi me ke kiʻekiʻe o ka hōʻike o ΔFosB i hōʻike i ka liʻiliʻi, ʻoi aku ka nui, i ka pale ʻana i kahi ʻāpana saccharin ma hope o ka hana hou ʻana i ka ʻehā. Nui kekahi mau wehewehe pono no kēia mau ʻike. ʻO ka mea maopopo loa, i hāʻawi ʻia i nā mea heluhelu, he mea paʻakikī kēia paradigm i ka aversive, ʻaʻole i uku ʻia, nā waiwai lāʻau (Nachman et al., 1970; Riley Tuck, 1985). ʻO Elevated ΔFosB, a laila, ʻaʻole wale e hoʻonui i ka pane ʻana i ka uku ʻana i nā waiwai o ka lāʻau lapaʻau, akā e hoʻēmi i ka pane ʻana i nā mea ʻona maikaʻi e hoʻohuli ai. Inā loaʻa kēia pilikia, a laila hiki ke manaʻo ʻia nā mau kiʻī a hoʻokiʻekiʻe ʻia ΔFosB e hōʻike i nā CTA e koi iki ʻia a LiCl ma kahi o nā kiʻi me ka hōʻike maʻamau o ΔFosB. No ka hoʻāʻo ʻana i kēia hypothesis, ua holo ʻia nā kiʻi like ʻole i loko o kahi ʻano hoʻokaʻawale ʻokoʻa a ka pehu a lākou i loaʻa ai i kahi 1 hr i loaʻa i kahi mākaʻi 0.1 M NaCl a a, ma hope koke iho, ua hōʻemi ʻia ka intraperitoneally me ka saline, 0.018 M LiCl, a i ʻole 0.036 M LiCl.

hana

Nā Kaupapa

ʻO nā kumuhana he 58 (29 overexpressed ΔFosB a me 29 maʻamau ΔFosB) kāne kāne NSE-tTA × TetOp-ΔFosB Line He mau kiʻina i hoʻohana ʻia ma ka Līʻike 1. Ua helu like ʻia nā kaole i ka hāʻawi ʻana i ka hoʻokaʻawale ʻeke ma mua o ka saccharin-saline a i ʻole saccharin-cocaine i waena o nā hui. I ka manawa hoʻokolohua, ua ʻike nui ʻia nā kiʻina i ka hui hoʻokolohua o ofFosB i ka striatum no kahi wikiō 17, a kaupaona nā kiʻika a pau ma waena o 31.7 a me 50.2 i ka hoʻomaka ʻana o ka hoʻokolohua. Ua hoʻokaʻawale ʻia lākou ma kahi ʻē a e mālama ʻia e like me ka mea i hōʻike ʻia ma luna nei.

i hoʻomākaukauʻia

ʻO ka ʻolua ka mea like me ka wehewehe o hoʻokolohua 1.

Ke Kaʻina hana

Kaupaona ʻia nā kumuhana āpau i hoʻokahi lā ma ke ao. No nā ana ʻana i ka palena palena, ua kau ʻia nā kiʻi a pau ma ka papaʻaina o ka wai i ho'ākāka ʻia ma luna nei (1 hr am a me 2 pm), me ka ʻole a make doxycycline e like me kēlā me kēia hui. Hoʻokumu ʻia ka helu intake a me ke paona kino no 1 pule. I ka hoʻāʻo ʻana, loaʻa nā kiʻi a pau 1 hr holo i ka 0.1 M NaCl i ke kakahiaka i ukali koke ʻia e ka maʻi intraperitoneal saline (n = 9 / cell), 0.018 M LiCl (n = 10 / cell), a i ʻole 0.036 M LiCl (n = 10 / hale). I loko o nā lālani, ʻo ka hopena o ka puhipuhi o kahi pākaʻi 0.009 M a LiCl i hoʻohālikelike ʻia i ka nui o 10 mg / kg pāka o ka cocaine (Grigson, 1997). Eia nō naʻe, ua hāʻawi ʻia i ka ʻike ma mua o nā kiʻina ma eksperiment 1 a me nā hōʻike e hōʻike nei ua hiki i kēlā mauʻike ma mua ke pale i ka hoʻomohala ʻana a me / a i ʻole ka hōʻike ʻana o ka hui ʻana o CS-unconditioned stimulus (US) ma hope.Kahiine et al., 2005), ua hoʻohana mākou i nā helu wai kiʻekiʻe ma LiCl (0.018 M a me 0.036 M). Ua loaʻa nā lāʻau hoʻōla i ke kinipōpō "48 hr no ʻelima mau ho'āʻo. Loaʻa i nā mea āpau a pau 2 hr hiki i ka dH2ʻO ʻoe a i ʻole 100 /g / ml doxycycline i kēlā me kēia ahiahi a me 1 hr manawa e hele ai i dH2ʻO ʻO a i ʻole 100 μg / ml doxycycline i kēlā me kēia kakahiaka ma waena o nā hoʻokolohua hoʻokolohua. Loaʻa iā NaCl mai Fisher Chemical, Pittsburgh, PA; Loaʻa ʻia ʻo LiCl mai ka Sigma Chemical Company, ʻo St. Louis, MO. Hāʻawi ʻia ka hopena NaCl ma ka mahana wela o ka lumi.

Nā hualoaʻa a me ka kūkā

Kikowaena CS

Ua hoʻohālikelike ʻia ka intake me ka hoʻohana ʻana i kahi 2 × 3 × 5 hoʻohui ʻatikala ANOVA maʻa (ʻano maʻamau no ka overexpression o ΔFosB), lāʻau lapaʻau (saline, 0.018 M LiCl, a i ʻole 0.036 M LiCl), a me nā hoʻāʻo ʻana (1 – 5). Ua mālama ʻia nā hoʻokolohua post hoc, kahi kūpono, e hoʻohana ana i nā hoʻokele Neuman-Keuls me kahi alpha o .05. Hōʻike ʻia ka hopena o ka overexpression o ΔFosB ma ke kula ʻo LiCl CTA Hōʻike 3.

Hōʻike 3 

Ka waiwai (± SEM) intake (ml / 1 hr) o 0.1 M NaCl ma hope o elima mau pualima me ka loaʻa ʻana o ka maʻi intraperitoneal o ka saline, 0.018 M LiCl, a i ʻole 0.036 M LiCl ma NSE-tTA × TetOp-ΔFosB Line A mau kiʻina me ka maʻamau (ʻaoʻao hema ) ai ʻole na luna (pololei panel) ...

Hōʻike nā hualoaʻa o ANOVA i kahi hopena koʻikoʻi o ka laikini lāʻau hoʻāla a × F(8, 204) = 5.08, p <.001, e hōʻike ana i nā ʻiole āpau, me ka nānā ʻole i ka manaʻo ΔFosB, pale i ka lawe ʻana o ka NaCl CS i hui pū ʻia me ka mea hana maʻi LiCl e pili ana i nā kumulāʻau saline. ʻAʻole like me ka ʻikepili kokain i hōʻike ʻia ma luna, ʻaʻole i hoʻokokoke ke ANOVA ʻekolu ala i ka helu helu (F <1). Hoʻohui ʻia, ʻaʻohe hopena koʻikoʻi o ka mālama ʻana (ie, doxy a wai paha; F <1), Hoʻoikaika × Hoʻohui hoʻokolohua (F <1), a i ʻole Ka mālama ʻana × ka launa ʻana o ka lāʻau.F <1). Eia nō naʻe, ke nānā ʻana i ka ʻike i hōʻike ʻia ma Hōʻike 3 manaʻo e hōʻike ʻia ana ka hopena o Lipress, e like me ka cocaine, i liʻiliʻi ʻia i ka mehe a exFosB. No laila, ua hoʻomaʻamaʻa mākou i nā hui i hoʻokaʻawale ʻē aʻe me ka hoʻohana ʻana i 3 × 5 hui manuahi ANOVA e ʻano like ʻole nā ​​lāʻau a me nā hoʻokolohua. Ua hoʻopaʻa ʻia nā hopena o kēia mau ANOVA i kahi hopena koʻikoʻi nui o ka laʻa no ka hoʻāla ʻia ʻana o ka lāʻau moʻo moʻo e hiki ai ke maʻamau. F(8, 100) = 3.48, p <.001, a me ka overexpressed, F(8, 108) = 2.19, p <.033, .FosB iole. Ua hōʻike ʻia nā hoʻokolohua post hoc i kahi hōʻemi nui o ka loaʻa ʻana o ka CS e ka lāʻau ʻoi loa o LiCl ma nā hoʻāʻo 3-5 no nā ʻiole maʻamau a ma nā hoʻāʻo 3 a me 4 no nāʻiole i hōʻike nui ʻia (ps <.05).

ʻOiai ka nui o ka pālahalaha kiʻekiʻe, ʻoi aku ka nui o nā helu LiCl ma mua o ka ʻike mākeke ma ka Hoʻolālā 1. Ka hoʻohālikelike ʻia i loko o Hōʻike 3 pili paha i ka mōʻaukala o ka paʻakai a i ʻole ka cocaine mālama i loko o ka hoʻokolohua 1. Ma kahi hana e hoʻāʻo ai i kēia hypothesis, ua hoʻomaʻamaʻa mākou i ka ʻikepili LiCl CTA me ka hoʻohana ʻana i kahi 2 × 2 × 3 × 5 hoʻohui ʻatikala ANOVA ʻokoʻa ka mōʻaukala (saline vs. kokainā), ka hana lapaʻau (maʻamau ma ka maʻamau o ΔFosB), ka lāʻau (saline, 0.018 ʻO M LiCl, a i ʻole 0.036 M LiCl), a me nā ʻaina (1-5). No ka maʻalahi, ʻo ka moʻolelo kokainina i hōʻike iki i ka awelika o ka ʻikepili mai ka meole me ka mōʻaukala o ka ʻike me ka 10 mg / kg a me ka kokona ʻo 20 mg / kg. E like me nā hopena o ka loiloi mua, ʻaʻole naʻe ka hopena o ka hui ʻehā i hiki ke loaʻa i ka helu statistic, F(8, 180) = 1.34, p = .22. A ʻo ka mōʻaukala saccharin-saline a saccharin-cocaine pasangan, a laila, hiki ke hāpai i ka hoʻololi ʻana i ka ʻikepili, akā ʻaʻole i like ke ʻano o ka hopena, a me ka hoʻopili ʻana o ka mōʻaukala ka mea i kōkua nui i ka hōʻike ʻana i nā kūlike statistically i ka nui o ka LiCl- Ka hūnā CTA ma waena o nā kahe ΔFosB maʻamau a me nā kiʻi me kahi overexpression o ΔFosB. Ma ka huina, ua hoʻopau ʻo LiCl i ka hoʻokomo ʻana o ka NaCl CS, a ʻoiai he kumu haʻahaʻa o ka hopena i hōʻemi ʻia i nā kiʻi ΔFosB overexpressing, ʻaʻole i pili ka ʻokoʻa ma waena o nā hui mālama i ka hopena statistic.

Lawe ʻia i nā hopena mai nā hoʻokolohua 1 a me 2 e hōʻike ana i nā kiʻina me ka kiʻekiʻe ΔFosB e hoʻopau nui i ka sac charin CS ma hope o ka pūlima sacaine-cocaine a me ka makemake e hoʻopau i ka nui o kahi NaCl CS ma hope o ka helu NaCL – LiCl. ʻO ka hona e hoʻopau i nā ʻoi aku o nā lāʻau pili i ka lāʻau lapaʻau (e like me ka eksperimento 1) hiki ke hopena o ka hoʻonui ʻana i ka naʻau i nā waiwai ʻala o ka saccharin a / a i ʻole ka NaCl CS no ka mea ua hoʻokiʻekiʻe ʻia nā pae kiʻekiʻe o ΔFosB e pili pū me ka ka hoʻonui i ka pane i nā uku kūlohelohe ʻē aʻe e like me nā pellets meaʻai (Olausson et al., 2006) ka holo holo ʻana (Werme et al. 2002). Hōʻike ka hoʻokō 3 inā paha kēia mau kiʻina me ka kiʻekiʻe o nā striatal kiʻekiʻe o ΔFosB e pane maikaʻi loa aku i nā waiwai maikaʻi loa o ka pakanui ʻana o ka sucrose a me ka paʻakai i loko o nā hoʻāʻo ʻana i ʻelua mau hue wai.

Hōʻike 3

Hoʻolālā ʻia ka hoʻokolohua 3 e nānā i ka hypothesis e hoʻemi ʻia ka hoʻemi ʻana o CS intake ma ka ʻāʻuhala exFosB ʻikena i ka Hoʻolālā 1 he hopena o ka hoʻonui ʻia ʻana o ka waiwai ʻike ʻike ʻole wale nō ka lāʻau lapaʻau o ka hōʻino, akā ʻo ka loiloi kūloko maoli. No ka loiloi i kēia hypothesis, ua hoʻohana mākou i hoʻokahi mau ʻano hōʻike hoʻoneʻe ʻelua a me ʻelua mau lua i ka hopena e pili ana i ka hopena o ka overexpression o ΔFosB ma kahi hoʻomehana o kahi hōʻeuʻeu (sucrose). Hoʻohui ʻia, i hāʻawi ʻia i ka makemake no kēia mau kiole e hoʻonoho ma luna o ka NaCl CS ma hope o nā huina NaCl – LiCl ma Experiment 2, ua hoʻohana nō mākou i hoʻokahi mau ʻano hoʻokahi a ʻelua mau ʻāpana huina e nānā ai i ka hopena o ka hoʻāla ʻia onFosB ma luna o kahi ʻano o ka nui o nā ʻano. nā ʻikepili hou aʻe "ʻōpala" NaCl. Ua nānā ʻia ʻekolu mau helu o NaCl (0.03 M, 0.1 M, a me 0.3 M) a me sucrose (0.01 M, 0.1 M, a me 1.0 M). Ua hypothesized inā inā ka kiʻekiʻe o ΔFosB e hoʻonui i ka waiwai o ka uku kūlohelohe, nui loa ka komo ʻana o ka sucrose i nā kiʻi hoʻokolohua a i like me nā kaohi.

hana

Nā Kaupapa

ʻO nā kumuhana he 28 (14 overexpressed ΔFosB a me 14 maʻamau ΔFosB) kāne kāne NSE-tTA × TetOp-ΔFosB Line He mau kiʻina i hoʻohana ʻia ma ka Līʻike 1. I ka manawa hoʻokolohua, loaʻa ka pōmole i ka hui hoʻokolohua i hōʻeha loa i ka ΔFosB i ka striatum no nā wiki 25 paha. Eia kekahi, ua ʻike mua nā kiʻī me nā saccharin-sukrose i loko o kahi hoʻokolohua anticipatory kūleʻa ʻole i hoʻokō ʻia (ʻo nā ʻāpana e kākoʻo ana i ka hopena anticipatory i nā kiʻī he mau hoʻokolokolo ʻia). Wehepaʻa nā Mice ma waena o 31.5 a me 54.5 g i ka hoʻomaka ʻana o ka hoʻokolohua. Hoʻopau ʻia lākou a mālama ʻia e like me ka mea i hōʻike ʻia ma mua.

i hoʻomākaukauʻia

ʻO ka ʻolua ka mea like me ka mea i wehewehe i loko o Ka Hoʻolālā 1.

Ke Kaʻina hana

Kaupaona ʻia nā kumuhana āpau i kēlā me kēia lā. Ma kahi o ka nohona 4 ka lā, ua loaʻa kēlā me kēia kiʻi i kahi 1 hr holo i ka dH2O i ke kakahiaka me 2 hr holo a i ke ahiahi. Holo i ka hoʻokolohua, me nā kiʻī kahi i hoʻokiʻekiʻe ʻia ΔFosB (n = 14) loaʻa dH2E hoʻihoʻi i ke ahiahi i kēlā me kēia ahiahi, a me nā mea kuʻi me ka normal ΔFosB (n = 14) loaʻa 100 μg / ml doxycycline. ʻEkolu mau paʻa o ka NaCl (0.03 M, 0.1 M, a me 0.3 M) a me sucrose (0.01 M, 0.1 M, a me 1.0 M) i hoʻohana ia ma tastants. Hāʻawi ʻia i kēlā me kēia kiʻi i nā isika i ka wana kakahiaka 1-hr no ka lā console 3. ʻO nā lā mua 2 ka hōʻike hoʻokahi o nā hue ʻeke o ka tastant a me ka lā 3rd i loaʻa i kahi hōʻike pākahi lua o ka tastant a me ka dH2O. Ua helu ʻia nā kūlana o nā hue he ʻoka, hema a ʻākau, ma loko o nā hui a ma waena o nā hōʻike ʻelua ʻelua i hōʻike. Hōʻalo ʻia nā mea hoʻonā i kahi piʻi piʻi, a ua hoʻāʻo ʻia ka pahuhopu o NaCl ma mua o ka sucrose. ʻElua dH2ʻO O-nā hoʻokolohua wale nō i hana ma waena o nā hoʻāʻo ʻana a NaCl a me sucrose. E ana ʻia ka intake i kēlā me kēia lā i kahi kokoke i 1 / 10 ml.

ʻIkeʻikepili

Ua hōʻike ʻia ka ʻikepili i ka hoʻohana ʻana t na loiloi me kahi alpha o .05.

Nā hualoaʻa a me ka kūkā

ʻO nā hōʻike mai nā kīʻaha kīʻaha lua he mau ʻatikala loa a, no laila, e hōʻike ʻia ma ʻaneʻi (ʻike Hōʻike 4). Hōʻike ʻia ka ʻimi i loko o ka wai aniani kahi mākaukau e like me ke kuhikuhi ʻana.

Hōʻike 4 

Hōʻailona (± SEM) intake (ml / 1 hr) kahi paʻa o nā kikowaena o NaCl (nā papa pae ʻeleʻele) a me ka sucrose (papa hana i lalo) ma dH2O i NSE-tTA × TetOp-ΔFosB Line He mau kiole me ka pākaukau maʻamau (mau panel hema) a i ʻole ka pae pae ʻākau (pololei panel) o ΔFosB ...

Nā koho NaCl

Ma kahi holoʻokoʻa, ka mōʻaukala o CTA aʻoi aku i ka hopena 0.1 M NaCl ma hope o nā papa i ke ana o nā wai ʻole o LiCl, ʻaʻole ia i pale i ka hōʻike ʻana o nā hana makemake-aversion i ka hoʻonui ʻana i ka hoʻoulu ʻana o NaCl i ka wā i hōʻike ʻia ai i loko o ka hōʻike intake. I nā kiʻī me ka normal ΔFosB (ʻaoʻao hema hema), ke kau ʻana o ka lua o nā mea i haʻahaʻa o NaCl (0.03 M a me 0.1 M) ʻaʻole i ʻokoʻa ma ka intake o ka dH.2O i nā pahu paʻi ʻelua (ps> .05). ʻO ke kiʻekiʻe kiʻekiʻe loa o NaCl (0.3 M), eia naʻe, ʻoi aku ka liʻiliʻi i makemake ʻia ma mua o dH2O (p <.0001), kūlike me ke ʻano aversive o kēia kūpili (ʻO Bachmanov, Beauchamp, & Tordoff, 2002). I nā kiʻī me ke kiʻekiʻe ΔFosB (pae ʻākau hema), ʻike ʻia kahi ʻano like me 0.3 M ka holo ʻana o NaCl (p <.01), e hōʻike ana i ka piʻi ʻana o ΔFosB ʻaʻole i hoʻololi iki i ka pane i kēia stimulus aversive. ʻO kahi hiʻohiʻona ʻokoʻa, pehea mau, i hana ʻia me nā haʻahaʻa haʻahaʻa o NaCl. Kahi kikoʻī, ua hōʻike nāʻiole me nā hiʻohiʻona kiʻekiʻe o ka ΔFosB i kahi makemake no nā haʻahaʻa 0.03 M a me 0.1 M o NaCl e pili ana i dH2O i nā pahu paʻi ʻelua (ps <.03). Ke kiʻekiʻena o ΔFosB, a laila, e hoʻoneʻe i ka makemake no nā haʻahaʻa haʻahaʻa o NaCl mai kūlike ʻole a makemake ʻia.

ʻO ke makemake makemake o Sukrose

Hoʻopili ʻia i ka hoʻohana ʻana t hōʻike i nā hoʻokolohua no ka hoʻohālikelike i hōʻike ʻia, ʻaʻole mahele like ka dHFosB, ka hoʻohana ʻana o ka mea haʻahaʻa o ka sucrose (0.01 M).2O (p = .82). Ke hoʻohālikelike nei, makemake nui ʻia ka 0.1 M a me 1.0 M sucrose concentrations e pili i ka dH2O (ps <.0001). I nāʻiole me ka ΔFosB kiʻekiʻe, ʻoi aku ka makemake o ka sukrosa ma mua o dH2E nā mahele holoʻokoʻa i hoʻāʻo ʻia (ps <.02). Hāʻawi kēia ʻike i ke kākoʻo no ka hopena e hoʻonui ka kiʻekiʻe o ΔFosB i ka makemake no nā makana kūlohelohe.

Kūkākūkā

Hōʻike ka ʻikepili i kēia ʻatikala e piʻi ana ka kiʻekiʻe o ΔFosB i ka striatum me ka hoʻomakeʻa a i hoʻopaʻa ʻia ʻo ka cocainin intakeuated. Hōʻalo kēia ʻike i kā mākou wānana mua e pono ai kēlā mau kiʻekiʻe e hoʻomaʻemaʻe i nā hopena hoʻomehana o ka niu. ʻO ka kikoʻī, ʻoi aku ka kiʻekiʻe o ΔFosB e hoʻonui i ka pono o ka lāʻau o ka hōʻino kino (Colby et al., 2003; Kelz et al. 1999), a me nā holoholona me ka addot-prone phenotype a i ʻole ka mōʻaukala o ka mālama me ka morphine maʻi (ʻo ia mau mea e hāpai ai i nā kiʻekiʻe o ΔFosB) hōʻike i ka nui o ka hōʻemi ʻana i ka lāʻau lapaʻau e pili ana i ka lawelawe o ka saccharin e pili ana i nā kāohi.ʻO Grigson & Freet, 2000; Grigson et al., 2001). Eia nō naʻe he mea nui ia e hoʻomaopopo ai, ʻaʻole i hāpai ʻia nā mea i loko o nā hoʻokolohua kahiko nei ʻaʻole i hoʻokiʻekiʻe ʻia ΔFosB, akā hui pū ʻia nō hoʻi ka nui o ka hoʻōla ʻana mai ka hopena i nā lāʻau hōʻeuʻeu a i ʻole mea hoʻohiki laʻa.Nestler, 1995, 2001b; ʻO Nestler & Aghajanian, 1997). Ua hoʻohālikelike ʻia kēia mau hoʻololi hou aʻe i ka hana a hōʻike i kahi hūnā i ka wā e hoʻāʻo nei i ka hoʻohalike ʻana i ke kuleana o ΔFosB, per se, i ka lāʻau hoʻokaumaha lāʻau e hoʻopau ai i ka hana a CS. Mālama ʻia kēia hūnā no kēia mau hoʻokolohua (ʻo ia hoʻi, ua like nā kumuhana a pau me ke kaawale o nā kiʻekiʻe ma ΔFosB), e ʻae ana i kahi kuhikuhi no ka hana hou o ka ʻ ofFosB i ka hanana. E like me ka mea i hōʻike ʻia ma luna nei, hōʻike nā kaikepili o kēia manawa i ka hoʻopaʻa ʻia ʻana o ka kokela i ka hoʻowalewale o ka saccharin intake ka mea i hoʻonaninani ʻia i ka striatal ΔFosB, akā ua ʻike ʻia ka hopena. Ke kiʻekiʻe o ΔFosB i ka striatum, a laila, e lawelawe ana e hōʻemi ma mua o ka hoʻoikaika ʻana i ka mālama o ka cocaine-induced ka hoʻohana ʻana i ka saccharin intake.

Nui nā ʻano wehewehe i ka hopena attenuated i hiki ke haʻalele ʻia me ka wikiwiki. ʻO ka mua, hiki iā ia ke hoʻohaʻahaʻa i nā kiʻekiʻe i ΔFosB i ka waiwai uku o ka cocaine. ʻAʻohe manaʻo like ʻole kēia i hāʻawi ʻia i nā puke nui e hoʻopili ʻia ana i ka ΔFosB i ka hoʻonui ʻia ʻana o ka loaʻa ʻana o ka loaʻa kālā o nā cocaine a me nā mea ʻokoʻa o ka hōʻino.Colby et al., 2003; Kelz et al., 1999; ʻO McClung & Nestler, 2003; McClung et al., 2004; Nestler et al., 2001, 1999). ʻO ka lua, hiki i ka attenuation ke hoʻohālike i nā ʻano ʻokoʻa i ka hoʻopaʻa ʻia ʻana o nā lāʻau lapaʻau a me nā hopena e pili ana i ka ΔFosB. Eia hou, ʻaʻole kākoʻo nā puke i kēia hiki no ka mea nāna nā kiʻī a me nā kiʻī e hōʻike nei i nā ʻano like ʻole i ka hoʻokaumaha ʻia o ka laʻana o CS intake (Grigson, 1997; ʻO Grigson & Twining, 2002; ʻO Risinger & Boyce, 2002) a me ka paʻa ʻana e ka ΔFosB (Kelz et al., 1999; Olausson et al., 2006; Werme et al., 2002; Zachariou et al., 2006). I ka mea hiki, hiki i ka pae kiʻekiʻe o ΔFosB ke hana i kahi nui o ka hui limahana a e ʻāpono i ka hana ʻana i ka cocaine-ʻano i hoʻokomo ʻia i ka waiwai kahe. ʻAʻole ʻike ʻia kēia hiki, no ka ʻike ʻole ʻia ʻana o kēia ʻano ʻano ʻike i ke aʻo ʻana a i ʻole hana o ka ʻano hana.Colby et al., 2003), a me ka loaʻa o ka C Lix-induced CTA, ʻaʻole i ʻokoʻa, nui, me he ʻano o ka haʻi ΔFosB expression ma eksperiment 2. ʻO ka mΔ overexpressing pōkole ka hana maʻamau i ka maze wai Morris a me nā wahi i makemake ʻia.Kelz et al., 1999).

Kēia manawa hou e hoʻāla ʻia e ka wehewehe CTA kuʻuna o ka ʻikepili ma eksperiment 1. ʻO ia, inā ka hoʻomau ʻana o kokoleka i ka hana ʻana i ka cue saccharin i hoʻolake ʻia e nā waiwai lāʻau ʻona, a laila e manaʻo kekahi e hoʻokiʻekiʻe ʻia ʻo ΔFosB i liʻiliʻi, ma ka liʻiliʻi, i ka hopena o kēia mau lāʻau lapaʻau paʻa. ʻO keʻano, aia kahi hōʻike e pili ana i nā lāʻau o ka hōʻino he mau mea hōʻalo. Ua hōʻike ʻia ka Cocaine e like me ka pane o ka leleBlanchard, Kaawaloa, Hebert, & Blanchard, 1999) a me nā hana ʻinoʻO Blanchard & Blanchard, 1999) ma nā kiʻi. ʻOiai naʻe, ua hōʻike ka hapanui o nā hōʻike no ka hōʻino ʻana o ka hōʻino ʻana i ka hoʻohana ʻana iā CS ma o ka uku ʻana i nā mea ʻona.ʻO Grigson & Twining, 2002; ʻO Grigson, Twining, Freet, Wheeler, & Geddes, 2008). No ka laʻana, nā leʻaleʻa o ka thalamus gustatory (Grigson, Lyuboslavsky, & Tanase, 2000; ʻO Reilly & Pritchard, 1996; Scalera, Grigson, & Norgren, 1997; Schroy et al., 2005) ʻo ka lime gustatory (thalamocorticol loop)ʻO Geddes, Han, & Grigson, 2007), ka manuahi cortex (ʻO Geddes, Han, Baldwin, Norgren, & Grigson, 2008; Mackey, Keller, & van der Kooy, 1986) hōʻalo i ka hoʻokaʻā ʻana o kahi c saccharin cue e ka sucrose a me nā mea hōʻino o ka hōʻino ʻia, akā ʻaʻole na LiCl. Pēlā nō, hōʻike aku nā ʻano kaila wīwī i ka ʻāʻī ʻana o ka hōʻino no ka hōʻino ʻana a i ʻole sucrose US, akā ʻaʻole no kahi LiCl US (Glowa, Shaw, & Riley, 1994; ʻO Grigson & Freet, 2000). Ua hōʻike ʻia nā ʻano like ʻole like me nā hana hoʻopulapula o ka mokuʻāina (Grigson, Lyuboslavsky, Tanase, & Wheeler, 1999) a ma nā kaole me ka moʻaukala morphine kūloko (Grigson et al., 2001). Eia kekahi, i loko o nā hoʻokolohua 3 a me 2, ʻaʻole i loaʻa ka hopena o ka kiʻekiʻe o ΔFosB i kēlā me ka wai ʻole o ka unconditioned a i ʻole ke pane ʻana i ka hoʻoulu kaua aversive, kēlā me kēia. No laila, pili i nā isika maʻamau, nā kiole me ka hoʻokiʻekiʻe ΔFosB i hōʻike i ka hoʻololi like i ka hāmeʻa ʻo 0.3 M NaCl ma ka Hoʻolālā 3 a me kahi hoʻohālikelike like ʻole a ka LiCl e pili ana iā CSCl ma eksperimentation 2.

Ke hōʻike nei kēia hōʻike hōʻike, ma kahi noiʻi hou i loaʻa ai he mau hōʻike hōʻike ʻana i ka cocaine-kukuna i ka manaʻo ʻana i ka cue a saccharin cue me ka hoʻomaka ʻana o kahi kūlana aversive maʻi.Wheeler et al., 2008). Hōʻike mākou i ka hoʻokaʻawale ʻana o ke ʻano aversive, ma ka hapa nui, e ka neʻe ʻana o kahi cue-induced withdrawal (Grigson et al., 2008; Wheeler et al., 2008). A laila hiki ke noʻonoʻo ʻia ka hoʻonui ʻana o ka ΔFosB i ka striatum i ka emi ʻana o ka pale ʻana i ka cue pili i ka lāʻau lapaʻau no ka mea ʻoi aku ka lāʻau lapaʻau i ka hoʻomohala ʻana i ka cue-induced withdrawal. ʻOiai hiki, hiki i kēia hopena ke paʻakikī i ka ʻae ʻia no ka mea i nā kiʻī, ʻoi aku ka nui o ka hoʻowalewale i ka CS (e like me ke piʻi ʻana o ka ʻano hoʻāla e hoʻihoʻi ʻana i ke ʻano)Wheeler et al., 2008). No laila, me ka hoʻohana ʻana i kēia loiloi, e paʻa ʻia mākou i ka manaʻo e ʻae ʻia nā kiʻi me ka kiʻekiʻe ΔFosB e pane nui i nā waiwai maikaʻi loa o ka lāʻau lapaʻau, e like me ka hōʻike ʻia, akā hōʻike pū ʻia nō hoʻi i nā cue-induced craving a haʻalele paha. ʻAʻole paha he mea maʻamau.

ʻO ka wehewehe nui loa e pili ana i ka hopena e pili ana i ka ʻike i kēia manawa ʻoiai ʻo ka piʻi ʻana o ΔFosB ka nui o ka hopena o ka cocaine i loko o kēia mau kiʻina, ua hoʻonui pū ʻia ka waiwai makana o ka saccharin. Inā i hoʻonui nui ʻia ʻo ΔFosB ka uku piha o ka saccharin a me ka cocaine like a me ka pane, ʻoi aku ka nui o ka uku o ka saccharin iʻoi aku ka nui (hoʻohālikelike ʻia me ka kokina) e like me ka ʻōlelo a Weber (ʻo ia ka hoʻoweliweli ʻana i ke ʻano o ka hoʻololi ʻana ma ka ikaika piha o ka hoʻoulu ʻana. ; Pūnaewele, 1846). ʻO ia ka hoʻonui ʻana i ka pili o CS palatability e hoʻohaʻahaʻa i ka ʻokoʻa pili i waena o nā uku a e loaʻa hoʻi i ka hopena hoʻohālikelike o ka uku.Flaherty Rowan, 1986; ʻO Flaherty, Turovsky, & Krauss, 1994). A kākoʻo hou ʻia kēia ʻikepili e ka puke ʻana e hōʻike ana i ka kiʻekiʻe o ka ΔFosB hoʻonui e pane ana i nā uku kūlohelohe. Penei ka holo ʻana,Werme et al., 2002) a me ka hoʻowalewale no nā hale ʻai meaʻai (Olausson et al., 2006) ua hoʻonui ʻia me ka piʻi kiʻekiʻe o ΔFosB. Eia kekahi, ʻike ʻia ka ʻike i loaʻa ma eksperiment 3 e hōʻike ana i ka kiʻekiʻe o ka ΔFosB ke hoʻonui i ka makemake no ka sucrose (0.03 M, 0.1 M, a me 0.3 M) a no nā haʻahaʻa haʻahaʻa o NaCl (0.01 a me 0.1 M) i nā hōʻike ʻelua-pahu me ka wai.

ʻO ka pahuhopu o kēia hoʻokolohua ʻo ia ka loiloi i ka hopena o kahi kiʻekiʻe ΔFosB i ka paradigm hoʻohālikelike uku uku, kahi ʻano hana i manaʻo e hoʻohālikelike i ka hoʻowalewale lāʻau lapaʻau kūlohelohe o nā uku kūlohelohe kanaka.Grigson, 1997, 2000, 2002; ʻO Grigson & Twining, 2002; Grigson et al., 2008). He mea maʻamau ka addiction kekahi mea pili i ka hanana, a me nā mea he nui i komo i ka hōʻike o ke kuhi lāʻau. Eia nō naʻe, ma ke kumu o ka puke o kēia manawa, ka kiʻekiʻe o ΔFosB i hoʻoiho ʻia e ka hōʻike kino ʻana i nā lāʻau hōʻino he mea e pono ai ke kuleana i ka manaʻo o ka hopena uku i ka lāʻau lapaʻau.Colby et al., 2003; Kelz et al., 1999) a ma ka pane ʻana no ka uku kūlohelohe (Olausson et al., 2006; Werme et al. 2002). Kūkulu kēia ʻatikala i ka hopena o ΔFosB i ka hoʻopili ʻana i kēia mau uku. ʻAʻole kū ʻia ka kiʻekiʻe o ΔFosB no ka hoʻohaʻahaʻa ʻana i ka lāʻau lapaʻau e hoʻemi ai i ka cue saccharin. I ka ʻoiaʻiʻo, e ʻokiʻoki i nā kiʻīwī i hoʻopaʻa ʻia i ka ʻekekema o ka saccharin cue kūpono. Eia nō naʻe, e hōʻike ana i kā mākou ikepili i ke kiʻekiʻe o ΔFosB ma striatum e kūʻē i kēia ʻano me ka hoʻēmi ʻana i ka ʻike ʻokoʻa ma waena o ka uku uku kūlohelohe a me nā lāʻau hōʻino. I ka hana ʻana, i nā isika me kēia phenotype i ʻoi aku ka palekana mai ka lāʻau i ka wā e hōʻike ʻia ana me nā makana kūlohelohe kūpono. Ma ke kākoʻo, ke komo ʻana i ka saccharin i ka nucleus e hoʻokūkū i ka pane dopamine i ka hoʻomaka ʻana o ka morphine i nā pāheʻe ʻo Sprague-Dawley (ʻO Grigson & Hajnal, 2007) a me ka wehe ʻana i nā lā i kēlā me kēia lā i kahi hopena palr a holrose e hoʻohaʻahaʻa i ka makemake o nā kahe e hana no ka cocaine i ka wā i loaʻa mua.ʻ ,lelo, 2007) No laila, ʻoiai ka mea kiʻekiʻe o ka ΔFosB e koho i ka mauʻu a me nā kiole i ka lawe ʻana i ka lāʻau lapaʻau ma ke ʻano o nā uku ʻē aʻe, pono ia e pale i ke kumumanaʻo mai ka lawe ʻana i ka lāʻau ma ke alo o kahi makana kūlohelohe kūpono.

mau hoomaikai ana

Ua kākoʻo ʻia kēia noiʻi e nā Public Health Service Grants DA09815 a me DA024519 a e ka PA State Tobacco Settlement Fund 2006 – 07.

E hoʻomaopopo '

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