Biological Basis of Conditioned Cues Effects on EtOH-Seeking

描述(申请人提供)：酒精中毒是一种慢性疾病，其特征是反复反复饮酒。复发的潜在诱因包括与过去饮酒有关的线索。随后暴露在这些刺激下可能会导致酒精渴望的状态，从而导致酒精对我们的恢复。这项提议的目标是确定条件性线索如何引发或抑制药物寻找的生物学基础。这项研究的长期目标是确定通过条件性线索调节乙醇寻找的神经回路。总体假设是，存在两个不同的系统，它们整合了促进或抑制寻找乙醇的环境线索，每个系统都由独立的神经回路和神经递质系统组成。这些假说将主要在酒精偏好(P)大鼠身上进行测试，这表明了高酒精饮酒行为和强烈的酒精寻求和复发行为。建议的实验将确定环境线索(条件性兴奋和条件性抑制)对语境诱导寻求表达的影响。拟议中的实验将确定暴露在促进或抑制乙醇寻求的条件性线索中的神经化学后果。此外，拟议的实验将确定通过呈现促进或抑制乙醇寻求的线索而激活的神经元的神经递质特征。进一步的实验将确定改变离散脑区候选受体的活性对条件性线索改变乙醇寻找能力的影响。了解酒精寻求行为背后的复杂因素，以及环境线索增强或抑制乙醇寻求的能力，将有助于制定治疗策略，以减少对酒精的渴求和酒精复发。

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.