Ontogeny of Catechol-O-Methyltransferase Expression in the Rat Prefrontal Cortex: Effects of Methamphetamine Exposure

Repeated use of methamphetamine (METH) is known to dysregulate the dopaminergic system and induce long-lasting changes in behavior, which may be influenced by sex and age of exposure. Catechol-o-methyltransferase (COMT) is an enzyme that is involved in the breakdown of catecholamines, and its role in dopamine clearance is thought to be especially important in the prefrontal cortex (PFC) where dopamine transporter expression is relatively scarce.

The first study in this report utilized a rat model to characterize the ontogeny of COMT protein expression in the PFC and nucleus accumbens (NAc) across adolescence, which is a developmental stage that has been shown to involve significant reorganization of dopaminergic innervation. Drug-naïve male and female Sprague-Dawley rats were sacrificed on postnatal day (P) 29, 39, 49, or 69, and expression levels of COMT protein within the PFC and NAc were analyzed via Western blot. A separate group of rats were injected daily from P40 to P48 (adolescence) or P70 to P78 (adulthood) with saline or 3.0 mg/kg METH and sacrificed on P49 or P79.

We found that COMT expression in the PFC increases across adolescence in a sex-dependent manner but does not significantly change in the NAc during this timeframe. While METH decreased COMT in adult rats of both sexes, METH increased COMT expression in the PFC of rats exposed in adolescence.

The results of this work suggest that exposure to METH during adolescence uniquely effects dopamine clearance within the PFC, potentially contributing to differences in neurobiological outcomes from METH use.