大鼠自我给药乙醇的辨别性刺激特性由GABA(A)和NMDA受体介导。
The discriminative stimulus properties of self-administered ethanol are mediated by GABA(A) and NMDA receptors in rats.
作者信息
Hodge C W, Cox A A, Bratt A M, Camarini R, Iller K, Kelley S P, Mehmert K K, Nannini M A, Olive M F
机构信息
Department of Neurology, Ernest Gallo Clinic and Research Center, University of California at San Francisco, 94608, USA.
出版信息
Psychopharmacology (Berl). 2001 Feb;154(1):13-22. doi: 10.1007/s002130000619.
RATIONALE
The neurobiological systems that mediate the discriminative stimulus effects of self-administered drugs are largely unknown. The present study examined the discriminative stimulus effects of self-administered ethanol.
METHODS
Rats were trained to discriminate ethanol (1 g/kg, IP) from saline on a two-lever drug discrimination task with sucrose (10% w/v) reinforcement. Test sessions were conducted with ethanol (0 or 10% v/v) added to the sucrose reinforcement to determine if self-administered ethanol would interact with the discriminative stimulus effects of investigator-administered ethanol, or with the ethanol-like discriminative stimulus effects of the GABAA-positive modulator pentobarbital or the non-competitive NMDA antagonist MK-801.
RESULTS
During a saline test session, ethanol (10% v/v) was added to the sucrose reinforcement. Responding by all animals began accurately on the saline-appropriate lever and then switched to the ethanol-appropriate lever after rats self-administered a mean dose of 1.2 +/- 0.14 g/kg ethanol. During cumulative self-administration trials, responding initially occurred on the saline lever and then switched to the ethanol-appropriate lever after ethanol (0.68 +/- 0.13 g/kg) was self-administered. Investigator-administered MK-801 (0.01-1.0 mg/kg, cumulative IP) and pentobarbital (0.3-10.0 mg/kg, cumulative IP) dose-dependently substituted for ethanol. When ethanol (10% v/v) was added to the sucrose reinforcer, MK-801 and pentobarbital dose-response curves were shifted significantly to the left.
CONCLUSIONS
Self-administered ethanol substituted for and potentiated the stimulus effects of investigator-administered ethanol, suggesting that the discriminative stimulus effects of self-administered ethanol are similar to those produced by investigator-administered ethanol. Self-administered ethanol enhanced the ethanol-like discriminative stimulus effects of MK-801 and pentobarbital, which suggests that the discriminative stimulus effects of self-administered ethanol are mediated by NMDA and GABAA receptors.
原理
介导自我给药药物辨别刺激效应的神经生物学系统很大程度上尚不清楚。本研究考察了自我给药乙醇的辨别刺激效应。
方法
在一项以蔗糖（10% w/v）强化的双杠杆药物辨别任务中，训练大鼠区分乙醇（1 g/kg，腹腔注射）和生理盐水。测试阶段在蔗糖强化物中添加乙醇（0或10% v/v），以确定自我给药的乙醇是否会与研究者给药的乙醇的辨别刺激效应相互作用，或与GABAA阳性调节剂戊巴比妥或非竞争性NMDA拮抗剂MK-801的类乙醇辨别刺激效应相互作用。
结果
在生理盐水测试阶段，向蔗糖强化物中添加乙醇（10% v/v）。所有动物在对应生理盐水的杠杆上准确开始反应，在大鼠自我给药平均剂量为1.2±0.14 g/kg乙醇后，反应切换到对应乙醇的杠杆上。在累积自我给药试验中，最初反应发生在对应生理盐水的杠杆上，在自我给药乙醇（0.68±0.13 g/kg）后，反应切换到对应乙醇的杠杆上。研究者给药的MK-801（0.01 - 1.0 mg/kg，累积腹腔注射）和戊巴比妥（0.3 - 10.0 mg/kg，累积腹腔注射）呈剂量依赖性替代乙醇。当乙醇（10% v/v）添加到蔗糖强化物中时，MK-801和戊巴比妥的剂量 - 反应曲线显著左移。
结论
自我给药的乙醇替代并增强了研究者给药的乙醇的刺激效应，表明自我给药的乙醇的辨别刺激效应与研究者给药的乙醇产生的效应相似。自我给药的乙醇增强了MK-801和戊巴比妥的类乙醇辨别刺激效应，这表明自我给药的乙醇的辨别刺激效应由NMDA和GABAA受体介导。
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