Abstract
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.
Highlights
Sexual behaviors are a complex, coordinated suite of actions that arise from the integration of psychological and physiological processes with external elements
The combination of METH and ovarian hormones enhances the measures of sexual motivation; we hypothesized that METH would converge with ovarian hormone actions to increase neuronal activity and induce neuroplasticity of the neurocircuitry that underlies sexual motivation and behavior
We have presented one model system in which we can further study the motivational aspects of sexual behavior
Summary
Sexual behaviors are a complex, coordinated suite of actions that arise from the integration of psychological and physiological processes with external elements. Progesterone and the activation of the PRs is necessary for the occurrence of the solicitation, proceptive, and paced mating behaviors (Boling and Blandau, 1939; Beach et al, 1942; Beach, 1976; Whalen, 1974; Fadem et al, 1979; Tennent et al, 1980; Edwards and Pfeifle, 1983; Olster and Blaustein, 1988; Blaustein, 2008) These hormones strongly affect the responses to olfactory and tactile stimuli, with modest effects on generalized arousal (Chu et al, 2015), providing evidence that the ovarian hormones contribute to the central motive state to modulate the incentive qualities of the male rat. Central motive state arousal to increase sexual motivation in a context-specific manner by potentiating the behavioral responses towards an incentive stimulus
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