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Methamphetamine-enhanced female sexual motivation is dependent on dopamine and progesterone signaling in the medial amygdala.

ABSTRACT: Methamphetamine (METH) is a psychomotor stimulant strongly associated with increases in sexual drive and impulsive sexual behaviors that often lead to unsafe sexual practices. In women METH users, such practices have been associated with increases in unplanned pregnancies and sexually transmitted diseases. Despite this significant heath concern, the neural mechanisms underlying this drug-sex association are not known. We previously established a rodent model of METH-facilitated female sexual behavior in which estradiol and progesterone interact with METH to increase motivational components of female behavior and neuronal activation in the posterodorsal medial amygdala (MePD) (Holder et al., 2010; Holder and Mong, 2010). The current study more directly examines the mechanisms underlying the drug-sex interaction. Here, we hypothesize that METH-induced increases in MePD dopamine signaling bridge the METH-hormone interaction. In support of this hypothesis, we found that excitotoxic lesions targeted to the MePD attenuated the METH-induced increases in proceptive behavior. Furthermore, infusion of a D1 agonist into the MePD increased proceptive behavior, while infusion of a D1 antagonist blocked the ability of METH to increase proceptive behaviors. Additionally, we found that METH-treatment increased progesterone receptor (PR) immunoreactivity in the MePD, suggesting an interaction between dopamine and progesterone signaling. Indeed, infusions of the PR antagonist, RU486, prevented METH-induced increases in sexual behavior. Thus, taken together, the current findings suggest that dopamine in the MePD modulates enhanced sexual motivation via an amplification of progesterone signaling and contributes to a better understanding of the neurobiology of drug-enhanced sexual behaviors.

SUBMITTER: Holder MK

PROVIDER: S-EPMC4291296 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Methamphetamine-enhanced female sexual motivation is dependent on dopamine and progesterone signaling in the medial amygdala.

Holder Mary K MK Veichweg Shaun S SS Mong Jessica A JA

Hormones and behavior 20141111

Methamphetamine (METH) is a psychomotor stimulant strongly associated with increases in sexual drive and impulsive sexual behaviors that often lead to unsafe sexual practices. In women METH users, such practices have been associated with increases in unplanned pregnancies and sexually transmitted diseases. Despite this significant heath concern, the neural mechanisms underlying this drug-sex association are not known. We previously established a rodent model of METH-facilitated female sexual beh ...[more]

PMID: 25448531

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Project description:IntroductionDifferent techniques have been used to identify the brain regions that control sexual motivation and sexual behavior. However, the influence of sexual experience on the activation of these brain regions in the same subject is unknown. Using manganese-enhanced magnetic resonance imaging (MEMRI), we analyzed the activation of brain regions in the sexual incentive motivation (SIM) and the partner preference PP (tests) on weeks 1, 5, and 10 in male rats tested for 10 weeks. AIM. In experiment 1, we analyzed the possible toxic effects of 16 mg/kg of MnCl2 on male sexual behavior, running wheel, and motor execution. In experiment 2, subjects were tested for SIM and PP using MEMRI.MethodsIn both experiments, a dose of 16 mg/kg (s.c) of chloride manganese (MnCl2) was administered 24 h before subjects were tested and placed immediately thereafter in a 7-Tesla Bruker scanner.ResultsIn experiment 1, the dose of 16 mg/kg of MnCl2 did not induce behavioral alterations that could interfere with interpreting the imaging data. In experiment 2, we found a clear preference for the female in both the SIM and PP tests. We found a higher signal intensity in the olfactory bulb (OB) in week 1 of the SIM test compared to the control group. We also found increased signal intensity in the socio-sexual behavior and mesolimbic reward circuits in the SIM test in week 1. In the PP test, we found a higher signal intensity in the ventral tegmental area (VTA) in week 10 compared to the control group. In the same test, we found increased signal intensity in the socio-sexual and mesolimbic reward circuits in week 5 compared to the control group. Cohen's d analysis of the whole brain revealed that as the subjects gained sexual experience we observed a higher brain activation in the OB in the SIM group. The PP group showed higher brain activation in the cortex and subcortical structures as they acquired sexual experience.DiscussionAs the subjects gain sexual experience, more structures of the reward and socio-sexual circuits are recruited, resulting in different, and large brain activations.

Dataset Information

Methamphetamine-enhanced female sexual motivation is dependent on dopamine and progesterone signaling in the medial amygdala.

Publications

Methamphetamine-enhanced female sexual motivation is dependent on dopamine and progesterone signaling in the medial amygdala.

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