Extinction of cocaine self-administration produces a differential time-related regulation of proenkephalin gene expression in rat brain
Extinction of cocaine self-administration produces a differential time-related regulation of proenkephalin gene expression in rat brain
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DOI：
10.1016/s0893-133x(01)00221-4
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发表时间：
2001-08-01
影响因子：
7.6
通讯作者：
Ambrosio, E
中科院分区：
文献类型：
--
作者：
Crespo, JA;Manzanares, J;Ambrosio, E
本研究用原位杂交组织化学方法检测了可卡因自我给药行为消失对大鼠尾壳核(ST)、伏隔核(ACC)、嗅结节(Tu)、梨状皮质(Pir)、下丘脑腹内侧核(VMN)和中央杏仁核(Ce)脑啡肽原(Penk)基因表达的时程影响。将72只同龄雄性Lewis大鼠随机分为三组，每组10只：(1)一次性静脉注射可卡因1 mg/kg(CONT)，(2)非随机注射(NONCONT)1 mg/kg可卡因(NONCONT)，或(3)注射生理盐水(生理盐水)。自我给药的大鼠被训练在FR5强化计划下自我给药，至少3周。在药物摄入量达到稳定的基线水平后，用生理盐水代替药物。在第一个灭绝期之后，又恢复了2周的可卡因自我给药。在末次给药结束后(第0天)和第二次消退期后1、5、10天，取各组动物脑组织进行原位杂交，消退期0、1、5、10天，可卡因组大鼠ST、ACC、Pir、Tu区Penk基因表达水平明显高于生理盐水组，CONT组Ce区在消退期第1、5、10天显著低于NONCONT组和生理盐水组。在VMN核内，CONT组与NONCONT组和生理盐水组相比，Penk基因表达也有所下降，但仅在第5天差异有统计学意义。这些结果提示可卡因依赖后Penk基因表达的变化可能与可卡因戒断状态有关。[神经精神药理学25：185-194,2001](C)2001年美国神经精神药理学院。爱思唯尔科学公司出版。
The purpose of this study was to examine the time course effects of extinction of cocaine self-administration behavior on proenkephalin (PENK) gene expression in caudate-putamen nucleus (ST), nucleus accumbens (Acc), olfactory tubercle (Tu), piriform cortex (Pir), ventromedial hypothalamic nucleus (VMN), and central amygdala (Ce) as measured by in situ hybridization histochemistry. Seventy-two littermate male Lewis rats were randomly assigned in triads to one of three conditions: (1) contingent intravenous self-administration of 1 mg/kg/injection of cocaine (CONT), (2) noncontingent injections of either I mg/kg/injection of cocaine (NONCONT); or (3) saline yoked (SALINE) to the intake of the self-administering subject. The self-administering rats were trained to self-administer cocaine under a FR5 schedule of reinforcement for a minimum of 3 weeks. After stable baseline levels of drug intake had been reached, saline was substituted for drug. Following this first extinction period, cocaine self administration was reinstated for an additional period of 2 weeks. Immediately after cessation of the last session of cocaine self-administration (day 0) and 1-, 5-, and 10-day after the second extinction period, animal brains in each triad were removed to be processed for in situ hybridization, PENK mRNA levels were significantly higher in the cocaine groups when compared with SALINE group in the ST, Acc, Pir, and Tu regions on days 0, 1, 5, and 10 of the extinction and lower in the Ce region of CONT group when compared to NONCONT and SALINE groups on days 1, 5, and 10 of the extinction period. In the VMN nucleus, PENK mRNA content in CONT group versus NONCONT and SALINE groups was also lower, but there were statistically significant differences only on day 5. These results suggest that changes in PENK gene expression after contingent cocaine administration might be involved in cocaine withdrawal states. [Neuropsychopharmacology 25:185-194,2001] (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.