Maladaptive Sex Behavior Following Concurrent Methamphetamine and Sexual Experience in Male Rats is Associated with Altered Neural Activity in Frontal Cortex (2017)

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Neuropsychopharmacology. 2017 Jan 4. doi: 10.1038/npp.2017.1.

Kuiper LB1,2, Frohmader KS3,4, Coolen LM1,3,4.

Abstract

The use of psychostimulants is often associated with hypersexuality, and psychostimulant users have identified the effects of drug on sexual behavior as a reason for further use. It was previously demonstrated that methamphetamine (Meth), when administered concurrently with sexual behavior show impairment of inhibition of sexual behavior in a conditioned sex aversion (CSA) paradigm where mating is paired with illness. This is indicative of maladaptive sex behavior following Meth and sex experience.

The present study examined the neural pathways activated during inhibition of sexual behavior and the effects of concurrent Meth and sexual behavior on neural activity in these pathways, using ERK phosphorylation (pERK) as neural activity marker.

First, exposure to conditioned aversive stimuli in males trained to inhibit sexual behavior in the CSA paradigm was shown to increase pERK expression in medial prefrontal (mPFC), orbitofrontal cortex (OFC) and areas in striatum and amygdala.

Second, effects of concurrent Meth and sex were tested in males that were exposed to 4 daily sessions of concurrent Meth (1 mg/kg) or saline and mating and exposed to CSA one week after last treatment. Meth and mating-treated males showed significant impairment in inhibition of mating, higher pERK expression under baseline conditions, and disrupted pERK induction by exposure to the conditioned aversive stimuli in mPFC and OFC.

Alterations of pERK were in CaMKII-expressing neurons, suggesting changes in projections of these areas. Together, these data show that concurrent Meth and mating experience causes maladapative sexual behavior that is associated with alterations in neural activation in mPFC and OFC.

PMID: 28051103

DOI: 10.1038/npp.2017.1