• Stimulus Specificity and the Roles of Progesterone and Dopamine Receptors in a Model of Methamphetamine-facilitated Female Sexual Motivation

      Rudzinskas, Sarah Anne; Mong, Jessica Aurora (2017)
      Methamphetamine (MA) is a psychomotor stimulant which, when abused, is reported to increase sexual drive in both men and women. The neurobiological mechanism underlying the effect of MA on sexual motivation is not well understood, especially in women. Our lab has recapitulated this effect in a rodent model, where combined administration of MA with estradiol and progesterone results in a significant increase in proceptive, or sexually motivated, behaviors in ovariectomized female rats. We have demonstrated that neurons in the medial amygdala (MeA) undergo activational changes after MA, as measured by cFos upregulation. The data in this thesis addresses two major remaining gaps in knowledge of both the model itself and the mechanism by which MA increases sexual motivation. First, I addressed whether increased proceptive behaviors are truly indicative of sexual motivation, or instead a manifestation of MA-induced generalized arousal. Here, I present data to support that MA-induced increases in proceptive behaviors are specific to a sexually relevant stimulus. Furthermore, my data implies that MA may heighten responsivity to specific, androgen-mediated, sexually relevant cues. Since the ovarian hormones estradiol and progesterone are essential for the full display of female sexual behaviors, I examined the progesterone receptor (PR), which is known to be necessary for proceptive behavior. Our previous findings had suggested progesterone signaling mechanisms were a likely downstream target of MA, as dopamine signaling can modulate them. Therefore, the second major question I addressed was whether the increase in PRs induced by MA in the MeA was sufficient for increasing sexual motivation, and whether this increase was directly due to dopamine receptor (D1R) activation. Now, I present data demonstrating that upregulation of PRs in the MeA is sufficient to increase sexually motivated and receptive behaviors in the absence of MA. This suggests that PR may be the feed-forward target of D1R-mediated facilitation of sexual motivation in females. However, my data does not support a direct link between D1R activation and PR upregulation. More surprisingly, neither D1R nor PR activation correlates with cFos levels in the MeA. Together, these data bring us closer to understanding the mechanism underlying MA-facilitated female sexual motivation.