Chronic cocaine treatment does not alter rat striatal D2 autoreceptor sensitivity to pergolide.

ABSTRACT

Rat superfused striatal slices, preloaded with [3H]dopamine, were electrically stimulated and the stimulation-induced outflow of radioactivity was taken as an index of dopamine release. In the presence of 10 microM nomifensine, exposure of striatal slices to unlabelled dopamine (0.3 microM) for 6 min prior to stimulation, significantly reduced stimulation-induced outflow. In contrast, a 21-min exposure to dopamine did not significantly alter stimulation-induced outflow. These results suggest that D2 receptors modulating dopamine release in the rat striatum may be rapidly desensitized in vitro. Rats were pretreated for 14 days with cocaine HCl (10 mg/kg/day i.p.) or saline. A progressive enhancement of locomotor activity in cocaine-treated rats over the pretreatment period compared to that in saline-treated rats indicated a behavioural sensitization to cocaine. The inhibitory effect of pergolide (1, 10 and 100 nM) on stimulation-induced outflow from striatal slices obtained from cocaine-pretreated rats was not different from that in slices obtained from saline-pretreated rats. Therefore no evidence was obtained for either a desensitization or a supersensitivity of striatal D2 autoreceptors by chronic cocaine administration.