Biological Basis of Conditioned Cues Effects on EtOH-Seeking

描述（由申请人提供）：酒精中毒是一种慢性疾病，其特征是反复发作的复发酒精消费。复发的潜在因素包括与过去饮酒配对的线索。随后暴露于这些刺激可能会诱发酒精渴望的状态，导致酒精使用的恢复。这个提议的目标是确定条件线索如何引起或抑制药物寻求的生物学基础。本研究的长期目标是确定调节条件线索对EtOH寻求的调节的神经回路。总体假设是，有两个不同的系统，整合环境线索，促进或抑制乙醇寻求，每个系统是由独立的神经回路和神经递质系统。这些假设将主要使用酒精偏好（P）大鼠进行检验，该大鼠表现出高度饮酒行为和稳健的EtOH寻求和复发行为。本实验旨在探讨环境线索（条件性兴奋和条件性抑制）对情境诱导寻求表达的影响。拟议的实验将确定暴露于促进或抑制EtOH寻求的条件线索的神经化学后果。此外，拟议的实验将确定神经元的神经递质特性激活的提示，促进或抑制乙醇寻求。进一步的实验将确定改变离散脑区中候选受体的活性对条件线索改变EtOH寻求能力的影响。了解EtOH寻求行为背后的复杂因素以及环境线索增强或抑制EtOH寻求的能力将有助于开发治疗策略以减少“渴望”和酒精复发。

DESCRIPTION (provided by applicant): Alcoholism is a chronic disorder characterized by repeated episodes of relapse to alcohol consumption. Potential precipitators of relapse include cues paired with past alcohol use. Subsequent exposure to these stimuli could induce a state of alcohol craving that results in reinstatement of alcohol us. The goals of this proposal are to determine the biological bases of how conditioned cues elicit or inhibit drug-seeking. The long- range objectives of this study are to determine the neurocircuits that regulate the modulation of EtOH-seeking by conditioned cues. The overall hypotheses are that there are two distinct systems that integrate environmental cues that promote or inhibit EtOH-seeking, and that each system is comprised of separate neurocircuits and neurotransmitter systems. These hypotheses will be tested primarily using the alcohol- preferring (P) rat, which demonstrates high alcohol drinking behavior and robust EtOH-seeking and relapse behaviors. Proposed experiments will determine the effects of environmental cues (conditioned excitation and conditioned inhibition) on the expression of context-induced seeking. Proposed experiments will determine the neurochemical consequences of exposure to conditioned cues that promote or inhibit EtOH-seeking. In addition, the proposed experiments will identify the neurotransmitter characteristics of neurons activated by presentation of cues that promote or inhibit EtOH-seeking. Further experiments will determine the effects of altering activity at candidate receptors in discrete brai regions on the ability of conditioned cues to alter EtOH- seeking. Understanding the complex factors that underlie EtOH-seeking behaviors and the ability of environmental cues to potentiate or suppress EtOH-seeking will contribute toward the development of therapeutic strategies to reduce 'craving' and alcohol relapse.