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

Abstract

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 and nucleus accumbens (NAC). Adult, male rats received bilateral injections of CTX (0–1 μg) 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 treatments. In both groups, locomotor responses to amphetamine (0.5 mg/kg, i.p.) were measured on experimental day 18. One day later, amphetamine-induced [ 3H]dopamine release was measured in tissue slices of the VTA and NAC. Amphetamine-induced locomotor activity was augmented in rats receiving 0.5 or 1.0 μg intra-VTA CTX pretreatment and the repeated amphetamine regimen. Amphetamine-induced [ 3H]dopamine release was increased from VTA but not NAC slices obtained from animals showing this behavioral sensitization. Thus, intra-VTA CTX treatment facilitates sensitization to low doses of repeated amphetamine which appears to be associated with the increased ability of this psychostimulant to release dopamine in the VTA.