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，以反复发作的酒精消费复发为特征。复发的潜在诱因包括与过去饮酒相关的线索。随后暴露于这些刺激可能会诱发一种酒精渴望状态，从而导致酒精的恢复。本建议的目标是确定条件线索如何引发或抑制药物寻求的生物学基础。本研究的长期目标是确定通过条件提示调节寻求etoh的神经回路。总的假设是，有两个不同的系统整合了促进或抑制etoh寻求的环境线索，每个系统都由独立的神经回路和神经递质系统组成。这些假设将主要使用酒精偏好(P)大鼠进行测试，该大鼠表现出高度饮酒行为和强烈的etoh寻求和复发行为。拟议的实验将确定环境线索（条件激发和条件抑制）对情境诱导寻求表达的影响。拟议的实验将确定暴露于条件提示促进或抑制etoh寻求的神经化学后果。此外，所提出的实验将确定神经元的神经递质特征，这些神经元被提示促进或抑制etoh寻求激活。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线索改变EtOH寻求能力的影响。了解寻求etoh行为背后的复杂因素，以及环境线索增强或抑制寻求etoh的能力，将有助于制定减少“渴望”和酒精复发的治疗策略。

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.