Repeated stimulation of the ventral tegmental area sensitizes the hyperlocomotor response to amphetamine

The locomotor-activating effects of amphetamine have been reported to increase with repeated drug administration. Although the precise underlying mechanisms for this behavioral sensitization effect remain unknown, many investigators have suggested a role for the mesolimbic dopaminergic system that emanates from cell bodies in the ventral tegmental area (VTA) of the midbrain. To test this hypothesis, the present study examined the effects of repeated electrical stimulation of the VTA (in place of repeated amphetamine administration) on the hyperlocomotor actions of d-amphetamine. Locomotor activity induced by 0.75 mg/kg SC amphetamine was assessed during two 90-min tests, one before and one after a 14-day treatment regimen during which animals experienced daily 15-min sessions of intracranial VTA stimulation. Each session involved the delivery of 600 trains of 0.5 s 60-Hz sine-wave stimulation applied at one of four intensities: 0, 15, 30, or 45 microA. An additional comparison group of rats self-administered 30 microA of VTA stimulation. Data analysis revealed that both the self-stimulation and the high current groups were reliably more active posttreatment compared to pretreatment. No such sensitization-like effects were observed in any of the other treatment groups. These results are consistent with the hypothesis that repeated activation of VTA neurons can produce a sensitization to the behavioral effects of d-amphetamine.