Department of Psychiatry and Behavioral Sciences and Department of Psychology and Neuroscience, Duke University Medical Center, Durham, NC 27710, USA.
Department of Psychiatry and Behavioral Sciences and Department of Psychology and Neuroscience, Duke University Medical Center, Durham, NC 27710, USA.
Eur J Pharmacol. 2014 Oct 5;740:53-7. doi: 10.1016/j.ejphar.2014.07.003. Epub 2014 Jul 10.
Neuroactive steroids can modulate a variety of neurobehavioral functions via the GABAergic system. This study was conducted to determine the importance of the neurosteroid pregnenolone on the regulation of alcohol intake. The effects of acute and chronic administration of pregnenolone on alcohol intake were assessed in alcohol preferring (P) rats. The rats were injected i.p. with the vehicle or pregnenolone (25, 50 or 75 mg/kg) and their alcohol and water intake were recorded at 2, 4, 6 and 24 h. Also, the chronic effects of 50 mg/kg (i.p.) pregnenolone on alcohol intake were determined. Our results show that although the main effect of i.p. injection of pregnenolone in reducing alcohol intake was not quite significant compared with the vehicle, pregnenolone at 75 mg/kg significantly (P<0.025) reduced alcohol intake. Regarding alcohol preference, acute administration of pregnenolone both at 50 mg/kg (P<0.05) and at 75 mg/kg (P<0.025) significantly reduced alcohol preference. In chronic experiments pregnenolone given for 10 consecutive days did not show a significant effect on alcohol intake and alcohol preference. Overall, although pregnenolone given i.p. acutely and significantly reduced alcohol intake and preference, the fact that chronic treatment did not show an effect diminishes its promise to be considered for the treatment of alcoholism. However, its profile of effects might be different in human alcoholics.
神经活性甾体可通过 GABA 能系统调节多种神经行为功能。本研究旨在确定神经甾体孕烯醇酮在调节酒精摄入中的重要性。通过在酒精偏爱（P）大鼠中评估孕烯醇酮的急性和慢性给药对酒精摄入的影响来确定其重要性。大鼠经腹腔注射给予载体或孕烯醇酮（25、50 或 75mg/kg），并在 2、4、6 和 24 小时记录其酒精和水的摄入量。此外，还确定了 50mg/kg（腹腔注射）孕烯醇酮对酒精摄入的慢性影响。我们的结果表明，尽管与载体相比，腹腔注射孕烯醇酮主要作用是减少酒精摄入，但与载体相比，75mg/kg 的孕烯醇酮可显著（P<0.025）减少酒精摄入。关于酒精偏好，急性给予 50mg/kg（P<0.05）和 75mg/kg（P<0.025）的孕烯醇酮均可显著降低酒精偏好。在慢性实验中，连续 10 天给予孕烯醇酮对酒精摄入和酒精偏好均无显著影响。总的来说，尽管腹腔内给予孕烯醇酮可急性和显著地减少酒精摄入和偏好，但慢性治疗没有效果的事实降低了其被认为是治疗酗酒的可能性。然而，其在人类酗酒者中的作用模式可能不同。
