CART peptides increase 5-hydroxytryptamine in the dorsal raphe and nucleus accumbens of freely behaving rats

Cocaine and amphetamine-regulated transcript peptides (CART) are implicated in the antidepressant effect. This may involve in 5-hydroxytryptamine (5-HT) in the CNS. The aim of the present studies was to investigate the effect of CART peptides on extracellular 5-HT in the dorsal raphe nucleus (DRN) and nucleus accumbens (NAcc) using a microdialysis approach in freely behaving rats. Reverse infusion of CART61−102 in the DRN produced a concentration (10-100 μM) -dependent increase in 5-HT in the DRN. Similarly, CART62-76 (10-100 μM) infused into the DRN and NAcc elevated 5-HT in the DRN and NAcc, respectively. Thus, CART increases extracellular 5-HT in both the DRN and NAcc. In addition, infusion of CART62-76 (100 μM) in the DRN produced a significant increase in 5-HT in the NAcc, implying an existence of CART receptors responsible for the depolarization-dependent release. In summary, the results of the present studies suggest that CART peptides may have an antidepressant effect through increases in extracellular 5-HT.