Adolescent nicotine exposure sensitizes cue-induced reinstatement of cocaine seeking in rats bred for high and low saccharin intake
Adolescent nicotine exposure sensitizes cue-induced reinstatement of cocaine seeking in rats bred for high and low saccharin intake
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DOI：
10.1016/j.drugalcdep.2011.02.016
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发表时间：
2011-10-01
影响因子：
4.2
通讯作者：
Carroll, Marilyn E.
中科院分区：
文献类型：
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作者：
Anker, Justin J.;Carroll, Marilyn E.
背景：早期药物暴露等环境因素会影响药物滥用的脆弱性，并且有证据表明药物滥用具有高度遗传性。本研究的目的是确定环境和遗传因素是否相互作用，从而产生附加的药物滥用脆弱性。方法：使用复发动物模型来研究青少年尼古丁暴露对高糖精摄入量（HiS）和低糖精摄入量（LoS）饲养的成年大鼠寻求可卡因的影响。来自 HiS 和 LoS 祖细胞系的大鼠接受皮下注射。注射尼古丁 10 天（产后第 22-31 天）。然后让大鼠成年并训练其按压杠杆以输注可卡因。在每次自我管理过程中，室内灯 (HL) 都会亮起，每次按下杠杆都会激活与杠杆 (LL) 相邻的一组灯。自我给予可卡因后，使 HL 和 LL 失活，用盐水代替可卡因溶液，并让大鼠停止按杠杆。随后，对大鼠进行了多组分恢复程序，包括：(1) 提示诱导的仅 LL 和单独 HL 的恢复，(2) 可卡因诱导的不存在 LL 和 HL 的恢复，(3) 以及可卡因诱导的 LL 存在的恢复。 结果：结果表明，当杠杆按下导致成年期的 HiS（而非 LoS）大鼠成年期接触尼古丁时，青少年尼古丁暴露对可卡因寻求的恢复敏感。 LL 提示演示。此外，在注射可卡因启动注射后，在青春期（LoS和HiS）暴露于尼古丁（相对于生理盐水）的大鼠在可卡因启动恢复条件下，当按下杠杆时，会寻求更多的可卡因。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
Background: Environmental factors such as early drug exposure influence drug abuse vulnerability, and evidence also suggests that drug abuse is highly heritable. The purpose of the present study was to determine whether environmental and genetic factors interact to produce additive drug abuse vulnerability.Methods: An animal model of relapse was used to examine the effects of adolescent nicotine exposure on adult cocaine seeking in rats bred for high (HiS) and low (LoS) saccharin intake. Rats from HiS and LoS progenitor lines received s.c. injections of nicotine for 10 days (postnatal days 22-31). Rats were then allowed to reach adulthood and were trained to lever press for cocaine infusions. During each self-administration session, the house light (HL) was illuminated and each lever press activated a set of lights adjacent to the lever (LL). Following cocaine self-administration, the HL and LL were deactivated, cocaine solutions were replaced with saline, and rats extinguished lever pressing. Subsequently, rats were tested under a multi-component reinstatement procedure consisting of: (1) cue-induced reinstatement with LL alone and the HL presented alone, (2) cocaine-induced reinstatement without LL and HL present, (3) and cocaine-induced reinstatement with LL present.Results: The results indicated that adolescent nicotine exposure sensitized the reinstatement of cocaine seeking during adulthood in HiS (but not LoS) rats when lever pressing resulted in LL cue presentations. In addition, following administration of the cocaine priming injection, rats exposed to nicotine (vs. saline) during adolescence (LoS and HiS) engaged in more cocaine seeking under the cocaine-primed reinstatement condition when lever pressing illuminated the LLConclusion: These results suggest that drug abuse vulnerability may be a function of early life exposure to drugs of abuse in addition to genetic influences. (C) 2011 Elsevier Ireland Ltd. All rights reserved.