A Role for the Preoptic Area in Modulating Cocaine Reward

描述（由申请人提供）：大多数研究指出，中皮质边缘多巴胺（DA）系统是描述可卡因奖励特性时必要的神经生物学终点;然而，该系统并不是孤立运行的，来自其他结构的输入可能在可卡因奖励中发挥重要作用。下丘脑内侧视前区（MPOA）是可卡因诱导活动的一个潜在调节器，但很少受到关注。MPOA参与两种自然奖励行为（母性行为和性行为）的调节，具有性二态性，并与中皮质边缘系统中的区域相互作用。因此，MPOA是调节可卡因诱导活性的神经解剖学位点的合乎逻辑的候选者，但令人惊讶的是，关于这种结构在药物滥用背景下的作用知之甚少。在这里，我们专注于可卡因奖励的临床前动物模型，假设MPOA调制可卡因诱导的活动中皮质边缘系统和奖励的行为表达，包括性别差异。这些研究将回答以下问题：（1）MPOA是否调节可卡因诱导的中脑皮质边缘系统神经元和多巴胺的活动？(2)MPOA调节可卡因奖赏吗？(3)含有性腺激素受体的MPOA中的细胞与中皮质边缘系统相互作用吗？(4)性腺激素是否通过MPOA调节可卡因诱导的中脑皮质边缘系统神经元和多巴胺活性？(5)性腺激素是否通过MPOA调节可卡因奖赏？使用神经解剖学，神经化学和行为分析，拟议的工作将检查MPOA是否可以作为一个扩展的奖励途径在调制可卡因诱导的活动。这些研究的结果将使我们对调节可卡因奖赏的神经化学和神经内分泌底物有更深入的了解。更好地了解可卡因奖赏的神经化学和神经内分泌调节将促进药物成瘾治疗的发展，此时激素因素可能特别重要。

DESCRIPTION (provided by applicant): Most studies point to the mesocorticolimbic dopamine (DA) system as the necessary neurobiological endpoint when describing cocaine's rewarding properties; however, this system does not operate in isolation, and input from other structures may play a significant role in cocaine reward. One area that has received little attention as a potential modulator of cocaine-induced activity is the medial preoptic area of the hypothalamus (MPOA). The MPOA is involved in the regulation of two naturally rewarding behaviors (maternal and sexual behaviors), is sexually dimorphic, and interacts with areas in the mesocorticolimbic system. As such, the MPOA is a logical candidate for a neuroanatomical locus modulating cocaine-induced activity, yet surprisingly little is known about the role of this structure in the context of drug abuse. Here, we focus on preclinical animal models of cocaine reward, hypothesizing that the MPOA modulates cocaine-induced activity in the mesocorticolimbic system and resulting behavioral expression of reward, including sex differences. The proposed studies will answer the following questions: (1) Does the MPOA modulate cocaine-induced neuronal and dopamine activity in the mesocorticolimbic system? (2) Does the MPOA modulate cocaine reward? (3) Do cells in the MPOA containing gonadal-hormone receptors interact with the mesocorticolimbic system? (4) Do gonadal hormones act via the MPOA to modulate cocaine-induced neuronal and dopamine activity in the mesocorticolimbic system? (5) Do gonadal hormones act via the MPOA to modulate cocaine reward? Using neuroanatomical, neurochemical, and behavioral assays, the proposed work will examine whether the MPOA may serve as an extension of the reward pathway in modulating cocaine-induced activity. The findings from these studies will yield a greater understanding of the neurochemical and neuroendocrine substrates regulating cocaine reward. A greater understanding of the neurochemical and neuroendocrine regulation of cocaine reward will facilitate the development of treatment for drug addiction, when hormonal factors may be especially important.