Intra-Ventral Tegmental Area Injection of Rat Cocaine and Amphetamine-Regulated Transcript Peptide 55-102 Induces Locomotor Activity and Promotes Conditioned Place Preference
by
Kimmel HL, Gong W, Vechia SD, Hunter RG, Kuhar MJ
Yerkes Regional Primate Research Center,
Emory University,
Atlanta, Georgia.
J Pharmacol Exp Ther 2000 Aug 1; 294(2):784-792


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 mug/side), an endogenously occurring peptide, dose dependently increased locomotor activity, whereas CART 1-26 (0.1-2.5 mug/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 mug/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 mug/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 mug/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.


CART
Cocaine
Dopamine
Metabolism
Comparison
Oral cocaine
Prenatal cocaine
Cocaine hotspots
The coke-craving brain
Freebasing flies go hyperkinetic
Cocaine, alcohol and cocaethylene
Cocaethylene and cocaine dependence

01 02 03 04 05 06 07 08 09 10 11 12
13 14 15 16 17 18 19 20 21 22 23 24


Refs
HOME
HedWeb
Future Opioids
BLTC Research
Wirehead Hedonism
Paradise-Engineering
Utopian Pharmacology
The Hedonistic Imperative
When Is It Best To Take Crack Cocaine?

swan image
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family