Effect of chronic cocaine treatment on D2 receptors regulating the release of dopamine and acetylcholine in the nucleus accumbens and striatum.

The inhibition of electrically stimulated [3H]DA and [14C]ACh release by a submaximal concentration of quinpirole was measured 1 week after pretreating rats for 9 days with cocaine (15 mg/kg IP, twice per day). Although this pretreatment significantly enhanced behavioral response to a challenge injection of cocaine when compared with rats pretreated with saline only, no significant differences were apparent in the degree of inhibition of electrically evoked [3H]DA or [14C]ACh release by quinpirole in either the nucleus accumbens or striatum. In addition, the potentiation of electrically evoked [3H]DA release and corresponding inhibition of [14C]ACh release by 10 microM cocaine, measured in striatal slices only, was not significantly different between the two treatment groups. These results suggest that the enhanced behavioral response resulting from chronic cocaine treatment (behavioral sensitization) is not caused by a subsensitivity of D2 terminal autoreceptors or by a supersensitivity of postsynaptic D2 receptors on cholinergic neurons.