CART peptide inhibits locomotor activity induced by simultaneous stimulation of D1 and D2 receptors, but not by stimulation of individual dopamine receptors.

CART (Cocaine- and amphetamine-regulated transcript) peptide has been implicated in playing a modulatory role in reward and reinforcement. Previously, our laboratory demonstrated that injections of CART peptide (CART 55-102) into the nucleus accumbens (NAc) attenuated both cocaine- and dopamine-induced increases in locomotor activity (LMA), and attenuated cocaine reward as well. In this study, the effects of CART peptide on LMA induced by dopamine receptor agonists were evaluated after intraaccumbal injections in male, Sprague-Dawley rats. Effects of the D1 receptor agonist SKF-81,297, saline, CART 55-102, or CART 55-102 and SKF-81,297 together were compared. The SKF-81,297-induced increase in LMA was potentiated by coadministration of CART, while injection of CART alone had no significant effect. Injection of the D2 agonist 7-OH-DPAT had no effect on LMA, and the combination of both 7-OH-DPAT and CART peptide also had no effect. Quinelorane, a D3 receptor agonist, did not alter LMA, nor did the combination of CART peptide and quinelorane. The next experiment examined the effects of CART peptide on LMA induced by coinjection of both the D1 agonist SKF-81,297 and the D2 agonist 7-OH-DPAT. The combination of SKF-81,297 and 7-OH-DPAT induced greater LMA than SKF-81,297 alone. Coadministration of CART peptide along with the D1 and D2 agonists reduced LMA. These results strongly suggest that CART peptide reduces the effects of psychostimulants by modulating the simultaneous activation of both D1 and D2 dopamine receptors rather than by affecting the action of any individual dopamine receptor.