Neuroscience Institute, Section of Cagliari, National Research Council of Italy, Monserrato, CA I-09042, Italy.
Department of Biomedical Sciences, University of Sassari, Sassari, SS I-07100, Italy.
Neuropharmacology. 2018 Jul 1;136(Pt A):146-158. doi: 10.1016/j.neuropharm.2017.10.012. Epub 2017 Oct 16.
Systemic administration of the orthosteric agonist, baclofen, and several positive allosteric modulators (PAMs) of the GABA receptor has repeatedly been reported to decrease operant oral alcohol self-administration in rats. The aim of the present study was to evaluate the contribution of the mesolimbic dopamine system to the reducing effect of baclofen and GABA PAMs on the reinforcing properties of alcohol. To this end, baclofen or the GABA PAM CGP7930 were microinjected into the ventral tegmental area (VTA) of selectively bred, Sardinian alcohol-preferring (sP) rats trained to self-administer alcohol. Baclofen (0, 0.03, 0.1, and 0.3 μg) or CGP7930 (0, 5, 10, and 20 μg) were microinjected via indwelling unilateral guide cannula aiming at the left hemisphere of the VTA. Treatment with baclofen resulted in a dose-related suppression of the number of lever-responses for alcohol and the amount of self-administered alcohol. No dose of baclofen altered rat motor-performance, evaluated by the inverted screen test immediately before the self-administration session. Treatment with CGP7930 halved the number of lever-responses for alcohol and amount of self-administered alcohol, with no effect on rat motor-performance. Site-specificity was investigated testing the effect of microinjection of baclofen and CGP7930 into the left hemisphere of deep mesencephalic nucleus: compared to vehicle, neither 0.3 μg baclofen nor 20 μg CGP7930 altered lever-responding for alcohol and amount of self-administered alcohol. Collectively, the results of the present study suggest the involvement of GABA receptors located in the VTA in the mediation of alcohol reinforcing properties in sP rats. This article is part of the "Special Issue Dedicated to Norman G. Bowery".
系统给予正构激动剂巴氯芬和几种 GABA 受体的正变构调节剂（PAMs），已被反复报道可减少大鼠操作性口腔酒精自我给药。本研究旨在评估中脑边缘多巴胺系统对巴氯芬和 GABA PAMs 降低酒精强化作用的贡献。为此，将巴氯芬或 GABA PAM CGP7930 微注射到选择性繁殖的萨丁岛酒精偏好（sP）大鼠的腹侧被盖区（VTA）中，这些大鼠被训练进行酒精自我给药。通过向 VTA 的左侧半球插入的单侧留置引导套管，微注射巴氯芬（0、0.03、0.1 和 0.3μg）或 CGP7930（0、5、10 和 20μg）。巴氯芬的剂量与酒精的杠杆反应次数和自我给药量呈剂量相关抑制。在自我给药前的倒置屏幕测试中，没有剂量的巴氯芬改变大鼠的运动表现。CGP7930 的处理使酒精的杠杆反应次数和自我给药量减少了一半，而对大鼠的运动表现没有影响。通过测试微注射巴氯芬和 CGP7930 到中脑深部核的左侧半球对酒精的杠杆反应次数和自我给药量的影响，研究了部位特异性：与载体相比，0.3μg 巴氯芬和 20μg CGP7930 均未改变酒精的杠杆反应次数和自我给药量。总的来说，本研究的结果表明，VTA 中的 GABA 受体参与了 sP 大鼠酒精强化作用的介导。本文是“专门献给 Norman G. Bowery 的特刊”的一部分。
