Implication of the GABA(B) receptor in gamma vinyl-GABA's inhibition of cocaine-induced increases in nucleus accumbens dopamine

Previously, we demonstrated that gamma vinyl-GABA (GVG, Vigabatrin(R)) dose -dependently inhibits cocaine-induced increases in dopamine (DA) concentrat ions in both the rodent and primate brain. Furthermore, it abolishes cocain e self-administration and conditioned place preference, while having no eff ect on locomotor activity or drug delivery to the brain. In an effort to be tter understand the mechanisms underlying this inhibition, we examined the effect of the selective GABA(B) receptor antagonist SCH 50911 on the GVG-in duced decrease in cocaine's elevation of extracellular DA concentrations in the nucleus accumbens (NACC). Cocaine administration alone (20 mg/kg i.p.) produced a 480% increase in extracellular NACC DA levels. GVG (300 mg/kg i .p.) significantly reduced this increase by 25% (P < 0.01). In sharp contra st, extracellular DA levels increased to 550% after the sequential administ ration of SCH 50911 (3 mg/kg i.p.), GVG, and cocaine. This increase is sign ificantly different than GVG and cocaine (P < 0.05) but similar to cocaine alone. These results demonstrate that the GABA(B) antagonist SCH 50911 was able to completely abolish GVG's inhibition of cocaine-induced increases in DA in the NACC and implicates the GABA(B) receptor in the mechanism underl ying this inhibition. Synapse 31:151-153, 1999. (C) 1999 Wiley-Liss, Inc.