Correlation between behavioral sensitization to cocaine and G protein ADP-ribosylation in the ventral tegmental area.
The ventral tegmental area is a site of action by psychostimulants in the production of behavioral sensitization. Recently, G proteins of the ventral tegmental area have been implicated in behavioral sensitization to cocaine. To further investigate the specific role of G proteins, rats were treated with either 15 or 30 mg/kg, i.p., of cocaine (x 5 days), and at 1, 6 or 24 h after the last injection in vitro pertussis toxin catalyzed adenosine diphosphate (ADP)-ribosylation was used to measure the G proteins in the ventral tegmental area, nucleus accumbens, prefrontal cortex, substantia nigra, and striatum. A significant decline in the ADP-ribosylation of G proteins, specific for the ventral tegmental area, was observed at 1 and/or 6 h but had returned to normal by 24 h. A significant negative correlation was found between the percent of G proteins ADP-ribosylated in the ventral tegmental area and the behavioral activity elicited in sensitized but not acute cocaine-treated animals at 1 h after injection. These data suggest that the G proteins ADP-ribosylated by pertussis toxin may be involved in the sensitized motor response produced by repeated cocaine administration in rats.
Striplin
C D
CD
Department of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman 99164-6520.
Kalivas
P W
PW
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000378:metabolism*
D000246:Adenosine Diphosphate Ribose; D019204:GTP-Binding Proteins; D003042:Cocaine