Rudzinskas Sarah A, Williams Katrina M, Mong Jessica A, Holder Mary K
Program in Neuroscience, University of Maryland, Baltimore, MD, United States.
Department of Veterans Affairs, Geriatric Research Education and Clinical Center, Baltimore, MD, United States.
Front Behav Neurosci. 2019 Sep 10;13:203. doi: 10.3389/fnbeh.2019.00203. eCollection 2019.
Methamphetamine (METH) is a psychomotor stimulant that is reported to enhance sexual desire and behavior in both men and women, leading to increases in unplanned pregnancies, sexually-transmitted infections, and even comorbid psychiatric conditions. Here, we discuss our rodent model of increased sexually-motivated behaviors in which the co-administration of METH and the ovarian hormones, estradiol and progesterone, intensify the incentive properties of a sexual stimulus and increases measures of sexually-motivated behavior in the presence of an androgen-specific cue. We then present the neurobiological mechanisms by which this heightened motivational salience is mediated by the actions of METH and ovarian hormones, particularly progestins, in the posterodorsal medial nucleus of the amygdala (MePD), a key integration site for sexually-relevant sensory information with generalized arousal. We finally demonstrate the cellular and molecular mechanisms underlying this facilitation of sexual motivation by METH, including the upregulation, increased phosphorylation, and activation of progestin receptors (PRs) in the MePD by METH in the presence of ovarian hormones. Taken together, this work extends our understanding of the neurobiology of female sexual motivation.
甲基苯丙胺（METH）是一种精神运动兴奋剂，据报道它会增强男性和女性的性欲及性行为，导致意外怀孕、性传播感染甚至共病精神疾病的增加。在此，我们讨论我们的增加性动机行为的啮齿动物模型，其中METH与卵巢激素雌二醇和孕酮共同给药，增强了性刺激的激励特性，并增加了在存在雄激素特异性线索时性动机行为的测量值。然后，我们介绍了神经生物学机制，通过该机制，METH和卵巢激素，特别是孕激素，在杏仁核后内侧核（MePD）中发挥作用，介导这种增强的动机显著性，MePD是性相关感觉信息与全身性唤起的关键整合位点。我们最终证明了METH促进性动机的细胞和分子机制，包括在存在卵巢激素的情况下，METH使MePD中的孕激素受体（PRs）上调、磷酸化增加并激活。综上所述，这项工作扩展了我们对女性性动机神经生物学的理解。
