Involvement of the Mesolimbic Dopamine System in Psychostimulant-Induced Hyperactivty

The mesolimbic dopamine system, which consists of the nucleus accumbens (NAc), the prefrontal cortex (PFc), and the ventral tegmental area (VTA), plays an important role in adaptive behavior in primates and rats. Although their precise role in behavior is not clear, previous studies suggest that NAc mediates hyper-locomotor activity induced by amphetamine (dopamine agonist). In the present study, we tested the hypothesis that NAc lesion would block amphetamine-induced hyperlocomotion. In addition, we examined effects of VTA and PFc lesions on amphetamine-induced hyperlocomotion. Wistar rats received either NMDA (10 µg/µl, 0.3µl/site) or sham lesions (saline, 0.3µl/site) in NAc, PFc, or VTA. A 14-day recovery period was allowed prior to testing in the open-field. Activity of the animal was measured by distance traveled. Data were recorded every 5 min for a 60 min period, spanning 3 days (baseline, vehicle, and amphetamine sessions). Baseline activity did not differ between lesioned rats and the controls. Following systemic amphetamine injection (1mg/kg, i.p.), rats with NAc lesions showed markedly suppressed locomotor activity compared to the control rats. Our hypothesis was supported by the present findings. VTA lesions produced a slight suppression of amphetamine-induced hyperlocomotion, whereas PFc lesion failed to do so. The present findings provide evidence that the NAc mediates amphetamine-induced hyperlocomotion. Given that NAc receives dopaminergic inputs from VTA, intact VTA may be required for expression of amphetamine-induced hyperactivity