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

The stable transcription factor Delta FosB is induced in the nucleus accumbens (NAc) by chronic exposure to several drugs of abuse, and transgenic expression of Delta 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 Delta FosB in dopamine D-1 receptor/dynorphin-containing striatal neurons to determine the effect of Delta 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 Delta FosB. Similarly, kappa opioid inhibition of adenylyl cyclase was enhanced in the Delta FosB expressing mice. In contrast, cannabinoid receptor-mediated signaling did not differ between mice overexpressing Delta FosB and control mice. These findings suggest that opioid and cannabinoid receptor signaling are differentially modulated by expression of Delta FosB, and indicate that Delta FosB expression might produce some of its effects via enhanced mu and kappa opioid receptor signaling in the NAc. (C) 2011 Elsevier Ltd. All rights reserved.