ROBUST SENSITIZATION TO AMPHETAMINE FOLLOWING INTRA-VTA CHOLERA-TOXINADMINISTRATION

Studies were conducted regarding the hypothesis that enhanced cAMP for mation in the ventral tegmental area (VTA) affects the magnitude of th e behavioral responses elicited by psychostimulant drugs. In the first paradigm, spontaneous and amphetamine-elicited locomotor activity was measured at various times following injection of cholera toxin (CTX), a known activator of adenylate cyclase, into the VTA. Adult male rats showed enhanced amphetamine-stimulated locomotor activity when tested 1 or 3 days after treatment with 0.5 mu g CTX into the VTA. Spontaneo us activity was markedly increased 1 and 3 days following treatment wi th the higher dose of 1.0 mu g CTX into the VTA, and amphetamine was s till capable of eliciting an increased level of locomotor activity abo ve this high baseline. Using a paradigm in which repeated amphetamine injections were given on an intermittent schedule following injection of CTX into the VTA, it was observed that a single low dose of ampheta mine (0.5 mg/kg) given 1 day after CTX (0.5 mu g) injection into the V TA led to a markedly potentiated locomotor activity response to subseq uent treatment with amphetamine. Evaluation of this protocol (initial amphetamine dose 24 h after CTX injection, and challenge treatment of amphetamine at various times thereafter) showed that the sensitization was long-lasting and could be observed after an initial dose of amphe tamine as low as 0.1 mg/kg. A sensitized response was also expressed w hen the challenge dose was given directly into the nucleus accumbens. These data suggest that injection of CTX into the VTA enhances the ind uction of locomotor sensitization to amphetamine. (C) 1997 Wiley-Liss, Inc.