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Vol. 294, Issue 2, 784-792, August 2000
Yerkes Regional Primate Research Center, Emory University, Atlanta,
Georgia
Cocaine- and amphetamine-regulated transcript (CART) is a novel mRNA
that has been reported to be increased by acute psychostimulant administration, and 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 fragments were bilaterally
injected into the ventral tegmental area. CART 55-102 (0.2-5.0
µg/side), an endogenously occurring peptide, dose dependently
increased locomotor activity, whereas CART 1-26 (0.1-2.5 µg/side;
not found endogenously) did not. The locomotor effects of CART 55-102 were dose dependently blocked by the dopamine D2 receptor
antagonist haloperidol (0.03-1.0 mg/kg i.p.). Four injections of 1.0 µg/side CART 55-102 induced a significant place preference,
suggesting that CART 55-102 is reinforcing. Increases in locomotor
activity after each of these CART 55-102 injections were similar and
did not show tolerance or sensitization. This treatment regimen of CART
55-102 also did not produce sensitization to locomotor activity after a
subsequent challenge with cocaine or amphetamine. When CART 55-102 (0.2-1.0 µg/side) was injected into the substantia nigra, no
significant change in motor activity was observed. However, a higher
dose of CART 55-102 (5.0 µg/side) induced a delayed increase in motor activity, suggesting a possible diffusion from the substantia nigra
into the ventral tegmental area. Our findings suggest that CART 55-102 is behaviorally active and may be involved in the actions of
psychostimulants. This is the first demonstration of the
psychostimulant-like effects of CART peptides.
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