Predominant D₁ Receptors Involvement in the Over-expression of CART Peptides after Repeated Cocaine Administration

Predominant D₁ Receptors Involvement in the Over-expression of CART Peptides after Repeated Cocaine Administration

The aim of this study was to investigate the involvement of dopaminergic receptors (DR) in behavioral sensitization, as measured by locomotor activity, and the over-expression of cocaine- and amphetamine-regulated transcript (CART) peptides after repeated administration of cocaine in mice. Repeated administrations of cocaine induced behavioral sensitization and CART over-expression in mice. The levels of striatal CART mRNA were significantly increased on the 3^rd day. CART peptides were over-expressed on the 5^th day in the striata of behaviorally sensitized mice. A higher proportion of CART^＋ cells in the cocaine-treated mice were present in the nucleus accumbens (NAc) shell than in the dorsolateral (DL) part of caudate putamen (CP). The concomitant administration of both D₁R and D₂R antagonists, SCH 23390 (D₁R selective) and raclopride (D₂R selective), blocked cocaine induced- behavioral sensitization, CART over-expression, and cyclic adenosine 5’-monophosphate (cAMP)/ protein kinase A (PKA)/phospho-cAMP response element-binding protein (<i>p</i>CREB) signal pathways. SCH 23390 more predominantly inhibited the locomotor activity, CART over-expression, <i>p</i>CREB and PKA activity than raclopride. Cocaine induced-behavioral sensitization was also attenuated in the both D₁R and D₂R knockout (KO) mice, respectively. CART over-expression and activated cAMP/PKA/<i>p</i>CREB signal pathways were inhibited in the D₁R-KO mice, but not in the D₂R-KO mice. It is suggested that behavioral sensitization, CART over-expression and activated cAMP/PKA/<i>p</i>CREB signal pathways induced by repeated administration of cocaine could be more predominantly mediated by D₁R.