Methamphetamine and Ovarian Steroid Responsive Cells in the Posteriodorsal Medial Amygdala are Required for Methamphetamine-enhanced Proceptive Behaviors

Katrina M Williams,Jessica A Mong

doi:10.1038/srep39817

Abstract

Methamphetamine (Meth) is a psychomotor stimulant strongly associated with increases in sexual drive and impulse in both men and women. These changes in sexual motivation have a greater impact on women due to their likelihood of facing the greater burden of unplanned pregnancies, as well as increased risk for psychiatric co-morbidities such as depression. We have previously established a rodent model of Meth-induced increases in sexual motivation. Using this model, we have identified the posteriodorsal medial amygdala (MePD) via excitotoxic lesion studies as a necessary nucleus in Meth-facilitated female sexual motivation. While lesion studies give us insight into key nuclei that may be targets of Meth action, such an approach does not give insight into the identity of the specific MePD neurons or neural circuitry involved in Meth-induced increases in proceptive behaviors. Using the DAUN02 inactivation method, a recently established technique for removing behaviorally relevant cell populations, we present evidence that the ovarian steroid/Meth responsive cells in the MePD are necessary for Meth-induced facilitation of proceptive behaviors. These findings form the basis for future work that will allow for the classification of neuronal subtypes involved in the MePD’s modulation of proceptive behavior as well as a stronger understanding of the neurocircuitry of female sexual motivation.

Highlights

Males but not toward castrate males[13]
We have adapted this model to test whether the Meth/estradiol benzoate (EB) +P responsive cells in the MePD are necessary for the associated increase in proceptive behaviors
Our goals are 1) to establish that cFos-lacZ transgenic rats exhibit Meth-induced MePD neuronal activation as well as increases in proceptive behaviors and 2) to demonstrate that Meth/EB +P responsive MePD neurons constitute a behaviorally relevant neuronal ensemble required for the Meth-facilitated increases in proceptive behaviors by removing these neurons with DAUN02 inactivation

Summary

Introduction

Males but not toward castrate males[13]. our work suggests a neurobiological correlate that underlies Meth-induced increases in proceptive behaviors. As β-gal expression is induced only in neurons with a strong activation of the cFos promoter and not in Fos negative or weakly activated neurons[14,19], this method is a powerful approach for testing whether activation of specific neuronal groups or ensembles are necessary for an associated behavior[14,15,19]. We have adapted this model to test whether the Meth/EB +P responsive cells (as measured by cFos expression) in the MePD are necessary for the associated increase in proceptive behaviors. Our goals are 1) to establish that cFos-lacZ transgenic rats exhibit Meth-induced MePD neuronal activation as well as increases in proceptive behaviors and 2) to demonstrate that Meth/EB +P responsive MePD neurons constitute a behaviorally relevant neuronal ensemble required for the Meth-facilitated increases in proceptive behaviors by removing these neurons with DAUN02 inactivation. Future studies will work to elucidate the cell types and circuitry associated with the behavioral modulation

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