环境线索诱导大鼠海洛因复吸行为模型建立

A rat model of heroin relapse behavior induced by drug-related environmental cues

目的建立环境线索诱导的大鼠海洛因复吸行为模型。方法训练雄性SD大鼠通过鼻触反应进行海洛因静脉自身给药 (每次剂量 0 .0 5mg/kg ,限量每日 2 5次 ) ,共 14d ,每天 4h。强化程序为累进比率。起始反应条件为 1,每 5次海洛因注射后增加 1,用灯光作为辨别和条件性刺激信号。停药两周后 ,大鼠重新返回实验笼进行复吸测试 ,连续两小时 ,前 1h为实验笼空间环境诱导 ,后 1h为条件性刺激诱导。结果训练 7d后大鼠建立稳定的海洛因静脉自身给药行为 ,获得 2 5次海洛因注射所需时间为 ( 165± 16)min ,有效鼻触反应为 ( 82± 5 )次。复吸测试时鼻触反应主要发生在有效鼻触 ,实验笼空间环境诱导的反应为 ( 2 8± 5 )次 ,条件性刺激为 ( 99± 10 )次。结论经过一段时间后 ,海洛因相关的空间环境和条件性刺激可以再次恢复大鼠原来的自身给药反应行为。该模型可用于环境因素诱导的复吸的神经生物学机制研究以及用于与反应恢复模型的比较 ,作为开发抗复吸模型的有效性有待进一步研究。

ObjectiveTo establish a rat model of heroin relapse behavior induced by drug-related environmental cues.MethodsMale SD rats were trained by nose-poke response to self-administer heroin (0.05 mg/kg, i.v., per infusion, limit 25 infusions per day) for 14 days of 4-hour training sessions daily. Reinforcement schedule was a progressive ratio, the response requirements for heroin infusions started with one, and increased one step after each five heroin infusions. Lights served as predictive discriminative stimulus and discrete conditioned stimuli. After two weeks of withdrawal, the rats were reintroduced to their training chambers for two consecutive 1-h relapse testing induced by contextual (chambers) and contingent discrete conditioned cues respectively.ResultsStable heroin self-administration behavior was established after 7 days of training, the time needed to earn the 25 heroin infusions were (165±16) min with (82±5) active nose-poke responses per session. Contextual and discrete conditioned cues induced response occurred mainly in the previous heroin-associated active nose-pokes, with total 1-h responses of (28±5) and (99±10) respectively.Conclusion Self-administration responding could be re-initiated by heroin-related contextual and conditioned cues after a period of abstinence from the drug environment in rats. The procedure used in this model may be useful for the study of the underlying mechanism of environmental cue induced relapse, and for comparing the effects of other manipulations known to affect behavior in the extinction/reinstatement model of relapse, its potential efficacy for screening anti-relapse medicine should be evaluated.