Effect of ?FosB overexpression on opioid and cannabinoid receptor-mediated signaling in the nucleus accumbens

The stable transcription factor ?FosB is induced in the nucleus accumbens (NAc) by chronic exposure to several drugs of abuse, and transgenic expression of ?FosB in the striatum enhances the rewarding properties of morphine and cocaine. However, the mechanistic basis for these observations is incompletely understood. We used a bitransgenic mouse model with inducible expression of ?FosB in dopamine D sub(1 receptor/dynorphin-containing striatal neurons to determine the effect of ?FosB expression on opioid and cannabinoid receptor signaling in the NAc. Results showed that mu opioid-mediated G-protein activity and inhibition of adenylyl cyclase were enhanced in the NAc of mice that expressed ?FosB. Similarly, kappa opioid inhibition of adenylyl cyclase was enhanced in the ?FosB expressing mice. In contrast, cannabinoid receptor-mediated signaling did not differ between mice overexpressing ?FosB and control mice. These findings suggest that opioid and cannabinoid receptor signaling are differentially modulated by expression of ?FosB, and indicate that ?FosB expression might produce some of its effects via enhanced mu and kappa opioid receptor signaling in the NAc.)