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，在描述可卡因的奖赏特性时，中皮质边缘多巴胺(DA)系统是必要的神经生物学终点；然而，该系统不是孤立运行的，来自其他结构的输入可能在可卡因奖赏中发挥重要作用。作为可卡因诱导活动的潜在调节器，下丘脑内侧视前区(MPOA)几乎没有受到关注。MPOA参与调节两种自然奖赏行为(母性行为和性行为)，是性二态的，并与中皮质边缘系统的区域相互作用。因此，MPOA是调节可卡因诱导活动的神经解剖学位点的合理候选者，但令人惊讶的是，人们对这一结构在药物滥用背景下的作用知之甚少。在这里，我们关注可卡因奖赏的临床前动物模型，假设MPOA调节可卡因诱导的中皮质边缘系统的活动，并由此产生奖赏的行为表达，包括性别差异。拟议的研究将回答以下问题：(1)MPOA是否调节可卡因诱导的中皮质边缘系统的神经元和多巴胺活动？(2)MPOA是否调节可卡因奖励？(3)含有性激素受体的MPOA中的细胞是否与中皮质边缘系统相互作用？(4)性腺激素是否通过MPOA作用于调节可卡因诱导的中皮质边缘系统的神经元和多巴胺活动？(5)性腺激素是否通过MPOA作用于调节可卡因奖励？利用神经解剖学、神经化学和行为分析，这项拟议的工作将检验MPOA是否可以作为调节可卡因诱导活动的奖励途径的延伸。这些研究的发现将使人们更好地理解调节可卡因奖励的神经化学和神经内分泌底物。更好地了解可卡因奖赏的神经化学和神经内分泌调节将有助于药物成瘾治疗的发展，因为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.