Microinjection of CART peptide 55-102 into the nucleus accumbens blocks both the expression of behavioral sensitization and ERK phosphorylation by cocaine.

The role of the biologically active CART 55-102 peptide in the nucleus accumbens (NAcc) in the expression of cocaine-induced behavioral sensitization was investigated. Rats were divided into four groups: one for saline and the other three for cocaine pre-exposures (15 mg/kg, i.p., once daily for 7 days). After 3 weeks of withdrawal, rats were microinjected into the NAcc either saline or CART 55-102 (1.0, or 2.5 microg/0.5 microl/side) followed by cocaine challenge (10 mg/kg, i.p.). Microinjection into the NAcc of CART 55-102 peptide dose-dependently blocked the expression of locomotor sensitization produced by repeated cocaine pre-exposures. Next, we further examined the effect of CART 55-102 microinjection on extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation levels in the NAcc. Additional four groups of rats were all cocaine pre-exposed and, after 3 weeks of withdrawal, they were either saline or cocaine challenged systemically following microinjection into the NAcc of either saline, CART 55-102 (2.5 microg/0.5 microl/side), or the equivalent mole amount of inactive CART 1-27 peptide. The increase of ERK1/2 phosphorylation levels in the NAcc by cocaine was completely blocked by CART 55-102 microinjection in this site, while it remains unaffected by inactive CART 1-27 peptide. These results suggest that CART 55-102 peptide in the NAcc may play a compensatory inhibitory role in the expression of behavioral sensitization by cocaine and these effects may be mediated by its inhibition of ERK1/2 phosphorylation in this site.