青少年尼古丁暴露会使高、低蔗糖摄入品系大鼠对线索诱导的可卡因觅药行为复发敏感。
Adolescent nicotine exposure sensitizes cue-induced reinstatement of cocaine seeking in rats bred for high and low saccharin intake.
机构信息
Department of Psychiatry, University of Minnesota, MMC 392, Minneapolis, MN 55455, USA.
出版信息
Drug Alcohol Depend. 2011 Oct 1;118(1):68-72. doi: 10.1016/j.drugalcdep.2011.02.016. Epub 2011 Mar 24.
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 LL.
CONCLUSION
These results suggest that drug abuse vulnerability may be a function of early life exposure to drugs of abuse in addition to genetic influences.
背景
环境因素，如早期药物暴露，影响药物滥用易感性，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产生叠加的药物滥用易感性。
方法
使用动物复吸模型来研究青春期尼古丁暴露对高（HiS）和低（LoS）蔗糖摄入大鼠成年可卡因寻求的影响。来自 HiS 和 LoS 亲代系的大鼠接受皮下注射尼古丁 10 天（出生后第 22-31 天）。然后，让大鼠成年并接受可卡因输注的杠杆按压训练。在每次自我给药期间，HL 灯点亮，每个杠杆按压激活与杠杆相邻的一组灯（LL）。可卡因自我给药后，HL 和 LL 熄灭，可卡因溶液用生理盐水替代，大鼠停止按压杠杆。随后，大鼠接受多成分复吸程序的测试，包括：（1）单独使用 LL 诱导线索复吸，单独呈现 HL；（2）没有 LL 和 HL 呈现时诱导可卡因复吸；（3）在存在 LL 时诱导可卡因复吸。
结果
结果表明，青春期尼古丁暴露使 HiS（而不是 LoS）大鼠在成年期可卡因寻求的复吸敏感化，当按压杠杆导致 LL 线索呈现时。此外，在给予可卡因引发注射后，青春期暴露于尼古丁（与生理盐水相比）的大鼠（LoS 和 HiS）在杠杆按压点亮 LL 时，在可卡因引发的复吸条件下表现出更多的可卡因寻求。
结论
这些结果表明，药物滥用易感性可能是除遗传影响外，早期暴露于滥用药物的功能。
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