Intra-ventral tegmental area injection of rat cocaine and amphetamine-regulated transcript peptide 55-102 induces locomotor activity and promotes conditioned place preference

Cocaine- and amphetamine-regulated transcript (CART) is a novel mRNA that h as been reported to be increased by acute psychostimulant administration, a nd that may be involved in the effects of psychostimulants. In this study, we examined the effect of centrally administered CART peptides on locomotor activity and conditioned place preference in the rat. CART peptide fragmen ts were bilaterally injected into the ventral tegmental area. CART 55-102 ( 0.2-5.0 mu g/side), an endogenously occurring peptide, dose dependently inc reased locomotor activity, whereas CART 1-26 (0.1-2.5 mu g/side; not found endogenously) did not. The locomotor effects of CART 55-102 were dose depen dently blocked by the dopamine D-2 receptor antagonist haloperidol (0.03-1. 0 mg/kg i.p.). Four injections of 1.0 mu g/side CART 55-102 induced a signi ficant place preference, suggesting that CART 55-102 is reinforcing. Increa ses in locomotor activity after each of these CART 55-102 injections were s imilar and did not show tolerance or sensitization. This treatment regimen of CART 55-102 also did not produce sensitization to locomotor activity aft er a subsequent challenge with cocaine or amphetamine. When CART 55-102 (0. 2-1.0 mu g/side) was injected into the substantia nigra, no significant cha nge in motor activity was observed. However, a higher dose of CART 55-102 ( 5.0 mu g/side) induced a delayed increase in motor activity, suggesting a p ossible diffusion from the substantia nigra into the ventral tegmental area . Our findings suggest that CART 55-102 is behaviorally active and may be i nvolved in the actions of psychostimulants. This is the first demonstration of the psychostimulant-like effects of CART peptides.