Article

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

Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30329, USA.
Journal of Pharmacology and Experimental Therapeutics (impact factor: 3.83). 09/2000; 294(2):784-92.
Source: PubMed

ABSTRACT 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 microg/side), an endogenously occurring peptide, dose dependently increased locomotor activity, whereas CART 1-26 (0.1-2.5 microg/side; not found endogenously) did not. The locomotor effects of CART 55-102 were dose dependently blocked by the dopamine D(2) receptor antagonist haloperidol (0.03-1.0 mg/kg i.p.). Four injections of 1.0 microg/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 microg/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 microg/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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Keywords

acute psychostimulant administration
 
amphetamine-regulated transcript
 
CART 55-102 injections
 
CART peptide fragments
 
cocaine
 
Cocaine-
 
conditioned place preference
 
delayed increase
 
dopamine D(2)
 
dose dependently
 
first demonstration
 
locomotor activity
 
locomotor effects
 
novel mRNA
 
possible diffusion
 
psychostimulant-like effects
 
subsequent challenge
 
substantia nigra
 
treatment regimen
 
ventral tegmental area