Optogenetic inhibition of the medial prefrontal cortex reduces methamphetamine-primed reinstatement in male and female rats.

Preclinical findings suggest sex-differences exist in drug-seeking behavior following methamphetamine (METH) self-administration. The medial prefrontal cortex (mPFC), is thought to contribute to the reinstatement of drug-seeking in males. Glutamatergic neurons project from the prelimbic portion of the mPFC to various brain regions modulating activity including the nucleus accumbens; thus the prelimbic region of the mPFC is thought to contribute to drug-seeking behaviors. Although studied in males, little research has investigated the role of the mPFC in females. The purpose of this study was to investigate if the prelimbic portion of the mPFC plays a role in METH-seeking behavior in both male and female rats. Animals were allowed to self-administer METH, and underwent extinction and two reinstatement sessions. Reinstatement sessions were counterbalanced such that optogenetic inhibition targeting the prelimbic cortex of the mPFC occurred only during one reinstatement session. Results revealed an increase in METH consumption during self-administration in male and female animals. During extinction, lever-pressing behavior decreased as training progressed. Under sham conditions, female rats exhibited significantly higher drug-seeking behavior during reinstatement. However, when optogenetic inhibition was applied, both male and female animals significantly decreased drug-seeking. In both males and females, the prelimbic portion of the mPFC plays an important role in drug-seeking behavior as related to METH-seeking.