Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA.
Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA.
Trends Pharmacol Sci. 2018 Aug;39(8):710-732. doi: 10.1016/j.tips.2018.04.003. Epub 2018 Jun 11.
In the past 20 years we have learned a great deal about GABA receptor (GABAR) subtypes, and which behaviors are regulated or which drug effects are mediated by each subtype. However, the question of where GABARs involved in specific drug effects and behaviors are located in the brain remains largely unanswered. We review here recent studies taking a circuit pharmacology approach to investigate the functions of GABAR subtypes in specific brain circuits controlling fear, anxiety, learning, memory, reward, addiction, and stress-related behaviors. The findings of these studies highlight the complexity of brain inhibitory systems and the importance of taking a subtype-, circuit-, and neuronal population-specific approach to develop future therapeutic strategies using cell type-specific drug delivery.
在过去的 20 年中,我们对 GABA 受体 (GABAR) 亚型有了很多了解,了解了哪些行为受到调节,哪些药物作用是由每种亚型介导的。然而,涉及特定药物作用和行为的 GABAR 位于大脑中的何处,这个问题在很大程度上仍未得到解答。我们在这里回顾了最近的研究,这些研究采用了电路药理学方法来研究控制恐惧、焦虑、学习、记忆、奖励、成瘾和应激相关行为的特定脑回路中 GABAR 亚型的功能。这些研究的结果强调了大脑抑制系统的复杂性,以及采用亚型、回路和神经元群体特异性方法来开发使用细胞类型特异性药物传递的未来治疗策略的重要性。