Methamphetamine enhances the motivation for female rat sexual behavior

描述（由申请人提供）：甲基苯丙胺是一种高度成瘾性的滥用精神兴奋剂，据报道，男性和女性服用者最显著的影响之一是性欲增加，对性的需求和紧迫感无法满足。此外，与使用可卡因和安非他明等其他精神兴奋剂的女性相比，女性冰毒使用者更有可能从事危险的性行为。提出的工作将检查甲基安非他明促进雌性大鼠动机性行为的分子基础。具体来说，这一建议侧重于内侧杏仁核，它接收来自VTA的多巴胺能输入。内侧杏仁核已被证明是大脑中关键的动机区域和性中心。本研究的具体目的是测试内侧杏仁核在甲基苯丙胺激活女性性回路中的作用，以及测试多巴胺在内侧杏仁核中介导性动机增强的作用。这项研究将在激素启动的雌性大鼠或油处理的对照组中进行，这些大鼠已经用甲基苯丙胺或生理盐水处理过。我们将利用免疫细胞化学的分子和细胞技术，实时RT-PCR，以及微量注射多巴胺或谷氨酸受体的药物阻滞剂和病变研究。这些目标将提供有关神经递质系统的作用的信息，这些作用可能是性动机增强的潜在基础，这可能对通过药物治疗甲基苯丙胺成瘾有影响。这项研究的潜在发现将促进我们对药物滥用在诱导性冲动和性行为方面的理解，这可能在危险性行为和疾病传播方面具有重要意义。在这个国家，从城市中心到农村城镇，甲基苯丙胺的使用正在成为一种流行病，破坏了家庭、社区和整个社会。使用甲基苯丙胺的动机之一是它能极大地增强性欲，这与性传播疾病和意外怀孕率的上升有关。这项旨在了解甲基苯丙胺增加性动机的方法的建议，可能有助于提供一条与甲基苯丙胺成瘾作斗争的途径。

DESCRIPTION (provided by applicant): One of the most striking effects reported by male and female users of methamphetamine, a highly addictive psychostimulant drug of abuse, is an increase in sexual libido and an insatiable need and urgency for sex. In addition, female methamphetamine users are more likely to engage in risky sexual behavior compared to female users of other psychostimulant drugs such as cocaine and amphetamine. The proposed work will examine the molecular underpinnings of the facilitation of motivated sexual behavior in the female rat by methamphetamine. Specifically, this proposal focuses on the medial amygdala, which receives dopaminergic input from the VTA. The medial amygdala has been shown to be a pivotal motivational area and sexual center in the brain. The specific aims of this proposal are to test the role of the medial amygdala in the activation of the female sexual circuitry by methamphetamine and to test the role of dopamine in the medial amygdala in mediating the enhancement in sexual motivation. This research will be conducted in hormonally-primed female rats, or oil-treated controls, that have been treated with methamphetamine or saline vehicle. We will utilize molecular and cellular techniques of immunocytochemistry, real-time RT-PCR, in addition to microinfusion of pharmacological blockers to dopamine or glutamate receptors and lesion studies. These aims will provide information regarding the actions of the neurotransmitter systems potentially underlying this enhancement of sexual motivation, which could have implications for the treatment of methamphetamine addiction via pharmacological agents. The potential findings of this research will advance our understanding of drugs of abuse in the induction of sexual drives and behavior, which could have important implications in terms of risky sexual behavior and disease transmission. Methamphetamine use in this country, from the urban centers to the rural towns, is becoming an epidemic that disrupts the family, the community, and society as a whole. One of the motivations for the use of methamphetamine is that it dramatically increases sexual libido, which has been linked to a rise in the rate of sexually transmitted diseases and unplanned pregnancies. This proposal, which seeks to understand the ways methamphetamine increases sexual motivation, may be useful in providing an avenue to combat methamphetamine addiction.