ROBUSTNESS OF G-PROTEIN CHANGES IN COCAINE SENSITIZATION SHOWN WITH IMMUNOBLOTTING

Daily cocaine administration has been shown to alter G proteins in mesolimbic nuclei, and these changes have been implicated in the initiation and expression of behavioral sensitization. To evaluate the robustness of changes in G proteins induced by daily cocaine treatments capable of producing behavioral sensitization, the levels of Gi1alpha, Gi2alpha, Go(alpha), Gs(alpha), and G(beta) protein were measured by immunoblotting at 1 hr after an acute injection of cocaine or saline given 1 or 14 days following the last injection of daily cocaine or saline. A significant decline in Gi1alpha was seen in the nucleus accumbens at 14 days following daily cocaine administration regardless of whether they received an acute challenge with cocaine or saline 1 hr prior to decapitation. No alterations were observed in the ventral tegmental area, substantia nigra, dorsolateral striatum, or prefrontal cortex in the levels of Gi1alpha, Gi2alpha, or Go(alpha). No change in G protein immunoreactivity was measured in the nucleus accumbens or ventral tegmental area of rats decapitated 1 hr after discontinuing daily cocaine. The possibility that a long-term change in Gi1alpha in the nucleus accumbens may be related to cocaine-induced behavioral sensitization is discussed.