Dissociation of the effects of amphetamine and quinpirole on dopamine release in the nucleus accumbens following behavioural sensitization

Abstract

Behavioural sensitization to the locomotor stimulant effect of (+)-amphetamine or quinpirole was induced in rats by intermittent drug administration. Once established, endogenous dopamine release (DA) was measured in slices containing nucleus accumbens using fast cyclic voltammetry. DA release induced by single pulse electrical stimulation did not differ between vehicle-, (+)-amphetamine-or quinpirole-treated groups. Multiple pulse stimulation resulted in enhanced DA release in quinpirole-sensitized rats and an attenuation of DA release in (+)-amphetamine-sensitized rats. In the presence of sulpiride, DA release was increased, at low stimulation frequencies, in vehicle- and quinpirole-treated animals, but not in amphetamine-treated animals. The sensitivity of axon terminal D2 DA receptors was assessed in vitro by measuring the concentration of quinpirole required to inhibit single pulse release of DA by 50% (EC(50)). Quinpirole EC(50) was significantly increased in the quinpirole-treated animals and significantly attenuated in the (+)-amphetamine-treated animals. The results suggest that the increase in DA release following quinpirole may arise from the desensitization of release-regulating D2 autoreceptors in the nucleus accumbens. The sensitization of axon terminal D2 autoreceptors and the decrease in DA release following behavioural sensitization with (+)-amphetamine is difficult to reconcile with a unitary explanation of behavioural sensitization to both quinpirole and (+)-amphetamine. It is suggested that the effects following (+)-amphetamine may be secondary to decreased axon traffic caused by DA displacement in the ventral tegmental area, and that the drugs examined in this study may induce behavioural sensitization by different mechanisms at different sites.