A Role for the Medial Preoptic Area in Regulating Gender-Sensitive Differences in

描述（由申请人提供）：男性和女性对可卡因的反应不同。尽管流行病学数据显示，滥用可卡因的男性多于女性，但有临床前和临床证据表明，女性更容易受到其精神兴奋剂作用的影响。证据还表明，雌激素至少在一定程度上造成了这种敏感性差异。大多数研究指出纹状体和伏隔核（NAcc）是雌激素作用产生这种性别差异的大脑区域。然而，有一个区域很少受到关注，因为它可能对调节这种效应很重要，那就是内侧视前区（MPOA）。MPOA是两性二态的，它参与调节自然奖励行为，是对雌激素活性最敏感的区域之一。这些特性使MPOA可能成为雌激素在可卡因反应中介导性别敏感差异的候选者。然而，人们对它在这种效应中的作用知之甚少。这些研究的目的是：(1)确定可卡因诱导的内侧视前核（MPN）激活是否具有性别二态性，以及是否由雌激素介导；(2)确定雌激素是否通过MPOA介导可卡因诱导的NAcc DA活性；(3)确定雌激素是否通过MPOA介导可卡因诱导的条件位置偏好，作为衡量可卡因奖励效应的指标。通过神经解剖学、神经化学和行为分析，本研究将研究雌激素是否通过MPOA增强女性对可卡因的反应。计划中的实验还将有助于更全面地了解下丘脑机制，特别是对性腺信号高度敏感的下丘脑机制如何影响对可卡因使用的反应。最后，通过探索一种可能的新机制，提出的研究将有助于我们更好地理解可卡因对性别敏感差异的神经内分泌调节。在设计成瘾治疗方法时，这种理解可能是有益的，因为性别敏感的差异尤其重要。拟议的研究将通过探索可能介导这种影响的新机制，帮助我们更好地了解可卡因反应中性别敏感差异的神经内分泌调节。在设计成瘾治疗方法时，这种理解可能是有益的，因为性别敏感的差异尤其重要。

DESCRIPTION (provided by applicant): Men and women respond differently to cocaine. Although epidemiological data show that more men than women abuse cocaine, there is preclinical and clinical evidence indicating that females are more vulnerable to its psychostimulant effects. Evidence also indicates that estrogen is at least partly responsible for this difference in sensitivity. Most studies point to the striatum and nucleus accumbens (NAcc) as brain areas on which estrogen acts to produce this gender difference. However, one area that has received little attention as potentially important for mediating this effect is the medial preoptic area (MPOA). The MPOA is sexually dimorphic, it is involved in regulating naturally rewarding behaviors, and it is one of the most sensitive regions to estrogen activity. These attributes make the MPOA a likely candidate in which estrogen might act to mediate gender-sensitive differences in response to cocaine. However, little is known about its role in this effect. The goals of these studies is: (1) to determine whether cocaine-induced activation of the medial preoptic nucleus (MPN) is sexually dimorphic, and whether it is mediated by estrogen; (2) to determine whether estrogen works via the MPOA to mediate cocaine-induced DA activity in the NAcc; (3) to determine whether estrogen acts via the MPOA to mediate cocaine-induced conditioned place preference, as a measure of cocaine's rewarding effects. Using neuroanatomical, neurochemical, and behavioral assays, the proposed work will examine whether estrogen enhances female1s response to cocaine via the MPOA. The planned experiments will also contribute to a more complete understanding of how hypothalamic mechanisms, especially one that is highly sensitive to gonadal signals, may affect response to cocaine use. Finally, the proposed studies will help us better understand the neuroendocrine regulation of gender-sensitive differences in response to cocaine, by exploring a possible new mechanism mediating this effect. Such an understanding may be beneficial when designing treatments for addiction, when gender-sensitive differences are especially important. PUBLIC HEALTH RELAVANCE The proposed studies will help us better understand the neuroendocrine regulation of gender-sensitive differences in response to cocaine, by exploring a possible new mechanism mediating this effect. Such an understanding may be beneficial when designing treatments for addiction, when gender-sensitive differences are especially important.