咖啡因对大鼠觅药行为的持久性和复燃的影响：与尼古丁相关线索的相互作用。
Effects of caffeine on persistence and reinstatement of nicotine-seeking behavior in rats: interaction with nicotine-associated cues.
机构信息
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
出版信息
Psychopharmacology (Berl). 2012 Apr;220(3):541-50. doi: 10.1007/s00213-011-2505-z. Epub 2011 Sep 27.
RATIONALE
Caffeine and nicotine are the most commonly co-used psychostimulants. However, it is still unclear whether caffeine exposure enhances nicotine-seeking behavior.
OBJECTIVE
The present study examined the effects of caffeine on nicotine-seeking in rats trained to self-administer nicotine with and without presession administration of caffeine.
METHODS
Male Sprague-Dawley rats were trained to intravenously self-administer nicotine (0.03 mg/kg/infusion, freebase) on a fixed ratio 5 schedule of reinforcement and associate a stimulus cue with each nicotine administration. Five minutes before the sessions, the rats received an intraperitoneal administration of caffeine (5 mg/kg). Extinction tests were conducted under four conditions: presession caffeine administration, response-contingent presentation of nicotine cues, neither condition, or both conditions. Reinstatement tests were conducted after responding was extinguished by withholding presession caffeine, nicotine, and its cues. A separate group of rats trained without presession caffeine exposure was also subjected to the reinstatement tests.
RESULTS
In the rats trained with presession caffeine exposure, continued caffeine administration sustained nicotine-seeking responses and interacted with nicotine cues to significantly delay the extinction of nicotine-seeking behavior. Readministration of caffeine after extinction effectively reinstated nicotine-seeking behavior. In caffeine-naive rats, caffeine administration did not reinstate extinguished nicotine-seeking behavior but significantly potentiated the cue-induced reinstatement of nicotine-seeking.
CONCLUSION
These data demonstrate that caffeine administration sustained and reinstated nicotine-seeking behavior, possibly via its acquired discriminative-stimulus properties predictive of nicotine availability. These findings suggest that smokers who attempt to quit may benefit from stopping caffeine consumption.
原理
咖啡因和尼古丁是最常被共同使用的精神兴奋剂。然而，目前尚不清楚咖啡因暴露是否会增强尼古丁觅药行为。
目的
本研究考察了咖啡因对接受过尼古丁自我给药训练的大鼠在给予咖啡因和不给予咖啡因前给药条件下的尼古丁觅药行为的影响。
方法
雄性 Sprague-Dawley 大鼠接受训练，以固定比例 5 的强化程序静脉内自我给予尼古丁（0.03mg/kg/次，游离碱），并将每个尼古丁给药与一个刺激线索相关联。在给药前 5 分钟，大鼠接受腹腔内给予咖啡因（5mg/kg）。在四种条件下进行了消退测试：前给药咖啡因、条件性呈现尼古丁线索、无条件或两种条件都有。在停止给予前给药咖啡因、尼古丁及其线索后，进行了复吸测试。一组未接受前给药咖啡因暴露的大鼠也接受了复吸测试。
结果
在接受过前给药咖啡因暴露训练的大鼠中，持续给予咖啡因维持了尼古丁觅药反应，并与尼古丁线索相互作用，显著延迟了尼古丁觅药行为的消退。在消退后给予咖啡因重新给药有效地恢复了尼古丁觅药行为。在咖啡因未暴露的大鼠中，咖啡因给药并未恢复消退的尼古丁觅药行为，但显著增强了线索诱导的尼古丁觅药的复吸。
结论
这些数据表明，咖啡因给药维持和恢复了尼古丁觅药行为，可能是通过其获得的区分性刺激特性来预测尼古丁的可用性。这些发现表明，试图戒烟的吸烟者可能会受益于停止咖啡因的摄入。
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