AMPHETAMINE-INDUCED SENSITIZATION AND RELEASE OF DOPAMINE IN SLICES FROM THE VENTRAL TEGMENTAL AREA OF RATS IS ENHANCED FOLLOWING ADMINISTRATION OF CHOLERA-TOXIN INTO THE VENTRAL TEGMENTAL AREA

Administration of cholera toxin (CTX) into the ventral tegmental area (VTA) markedly potentiates the development of behavioral sensitization to amphetamine. Experiments were conducted to determine whether this phenomenon is associated with altered dopamine release from the VTA an d nucleus accumbens (NAG). Adult, male rats received bilateral injecti ons of CTX (0-1 mu g) or its vehicle into the VTA. Half of the animals then received four injections of amphetamine (0.5 mg/kg, i.p.) given every other day, while the other half received no additional treatment s. In both groups, locomotor responses to amphetamine (0.5 mg/kg, i.p. ) were measured on experimental day 18, One day later, amphetamine-ind uced [H-3]dopamine release was measured in tissue slices of the VTA an d NAG. Amphetamine-induced locomotor activity was augmented in rats re ceiving 0.5 or 1.0 mu g intra-VTA CTX pretreatment and the repeated am phetamine regimen. Amphetamine-induced [H-3]dopamine release was incre ased from VTA but not NAC slices obtained from animals showing this be havioral sensitization. Thus, intra-VTA CTX treatment facilitates sens itization to low doses of repeated amphetamine which appears to be ass ociated with the increased ability of this psychostimulant to release dopamine in the VTA. (C) 1997 Elsevier Science Ireland Ltd.