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.