Phencyclidine-induced locomotor activity in the rat is blocked by 6-hydroxydopamine lesion of the nucleus accumbens: Comparisons to other psychomotor stimulants

The present study was primarily designed to explore the relationship between phencyclidine(PCP)-induced hyperactivity and the mesolimbic dopamine (DA) system. In addition, the motor-activating and behavioral effects of amphetamine (1.5 mg/kg), SKF-10,047 (25.0 mg/kg), scopolamine (1.0 mg/kg), and caffeine (10.0 mg/kg) were also measured and compared to PCP action. While all compounds produced a moderate to large degree of hyperactivity with varying time courses for effect, gross behavioral observations indicated a greater similarity between PCP and SKF-10,047 than between any of the other drugs. Following bilateral 6-hydroxydopamine lesions of the nucleus accumbens the robust locomotor-stimulating action of 5 mg/kg PCP was significantly reduced. Such lesions also successfully prevented amphetamine- and SKF-10,047-induced hyperactivity, but not the behavioral activation produced by scopolamine or caffeine. These results suggest that PCP and SKF-10,047, like amphetamine, elicit locomotor activity through presynaptic DA mechanisms within the mesolimbic system.