A Role for the Preoptic Area in Modulating Cocaine Reward

描述（由申请人提供）：在描述可卡因的奖励特性时，大多数研究指出中皮质边缘多巴胺（DA）系统是必要的神经生物学终点；然而，这一系统并非孤立运作，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）是一个很少受到关注的区域，作为可卡因诱导活动的潜在调节剂。MPOA参与调节两种自然奖励行为（母性行为和性行为），是两性二态的，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位点的逻辑候选者，然而令人惊讶的是，关于该结构在药物滥用背景下的作用知之甚少。在这里，我们将重点放在可卡因奖励的临床前动物模型上，假设MPOA调节可卡因诱导的中皮质边缘系统活动，并导致奖励的行为表达，包括性别差异。提出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性？(2) MPOA是否调节可卡因奖励？(3)含有性腺激素受体的MPOA细胞是否与中皮质边缘系统相互作用？(4)性激素是否通过MPOA调节可卡因诱导的中皮质边缘系统神经元和多巴胺活性？(5)性激素是否通过MPOA调节可卡因奖励？通过神经解剖学、神经化学和行为分析，本研究将研究MPOA是否可能作为奖赏通路的延伸，调节可卡因诱导的活动。这些研究的发现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。当激素因素可能特别重要时，对可卡因奖赏的神经化学和神经内分泌调节的更深入了解将促进药物成瘾治疗的发展。

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.