GABA RECEPTORS IN ETHANOL PLACE PREFERENCE AND AVERSION

被提议的项目的广泛的、长期的目标是调查 对于GABA神经递质系统在调节奖赏和 乙醇的厌恶特性。拟议的研究将利用 位置条件反射范式考察条件反射的习得 DBA/2J的位置偏好(CPP)和条件性位置厌恶(CPA) 老鼠。位置条件作用过程为研究提供了一个有用的模型 环境刺激物和药物之间的已知联系 奖励和厌恶的影响，并允许调查 位置习得中的特定神经通路 条件反射。尽管GABA系统被认为参与了 乙醇的许多行为影响，它还没有被调查为 可能是乙醇诱导的CPP或CPA的调节剂。的具体目标 这个项目是为了测试不同剂量的药理拮抗剂 GABAA和GABAB受体亚型在获得GABAA和GABAB中的选择性 乙醇诱导的CPP和CPA。这些研究将有助于阐明这一角色 GABA在调节条件性反应获得中的作用 乙醇的神经药理作用。总体而言，获得的信息 将有助于理解 乙醇激励作用的神经化学底物。 像这样的研究是重要的，以便开发适当的 人类寻求酒精和成瘾行为的临床治疗。

The broad, long-term goal of the proposed project is to investigate a role for the GABA neurotransmitter system in modulating the rewarding and aversive properties of ethanol. The proposed studies will utilize the place conditioning paradigm to examine the acquisition of conditioned place preference (CPP) and conditioned place aversion (CPA) in DBA/2J mice. The place conditioning procedure provides a useful model to study the learned association between environmental stimuli and a drug's rewarding and aversive effects, and allows for the investigation of specific neural pathways involved in the acquisition of place conditioning. Although the GABA system has been implicated in mediating many of ethanol's behavioral effects, it has not yet been investigated as a possible modulator of ethanol-induced CPP or CPA. The specific aims of this project are to test various doses of pharmacological antagonists selective for GABAA and GABAB receptor subtypes in the acquisition of ethanol-induced CPP and CPA. These studies will help elucidate the role of GABA in modulating the acquisition of conditioned responses to ethanol's neuropharmacological effects. Overall, the information gained from this project will contribute to an understanding of the neurochemical substrates underlying the motivational effects of ethanol. Studies such as these are important in order to develop appropriate clinical treatments for ethanol-seeking and addictive behavior in humans.