CAVEOLIN-1 MEDIATED SIGNALING HIGHLIGHTS SEX DIFFERENCES IN COCAINE DRUG ADDICTION

Caveolin-1 (Cav1) is an integral membrane protein that regulates intracellular signal transduction. Recent studies suggest that Cav1 overexpression in the hippocampus increases structural plasticity underlying learning and memory. Because this plasticity parallels that seen in the nucleus accumbens (NAc) during addiction to drugs of abuse, we were interested in whether Cav1 overexpression in this brain region would affect corresponding behavioral output. Specifically, we hypothesized that virally-mediated overexpression of Cav1 in the NAc of rats would increase psychostimulant-induced behavioral sensitization. Moreover, because prior studies have indicated that females exhibit enhanced responsiveness to psychostimulants in comparison to males, we investigated both male and female rats to identify whether Cav1 would have sex-dependent effects on responses to cocaine. To test this, we measured the progressive amplification of locomotor activity in response to repeated low-dose cocaine administration following intracranial injections of either neuron-specific Cav1 or an RFP control virus. In females, Cav1 overexpression promoted sensitization, as evidenced by an increase in locomotor activity from the first to last day of treatment, when compared to control animals. We also observed that Cav1 overexpression eliminated the reduction in weight gain that normally occurs with cocaine administration. Conversely, these effects of Cav1 were absent in males. Considered together, these data indicate that sex plays an important role in how Cav1 mediates cellular organization and signaling pathways within the functional output region of the NAc. Such results emphasize the importance of studying both sexes in biomedical research.