INVOLVEMENT OF D-1 AND D-2 DOPAMINE SYSTEMS IN THE BEHAVIORAL-EFFECTSOF COCAINE IN RATS

Cocaine (5-40 mg/kg, intraperitoneally) enhanced locomotion and rearin g accompanied with head circling and body shaking. Although at 40 mg/k g typical stereotypy licking occasionally appeared, 40% of the rats di ed. At doses that did not affect physiologic locomotion and rearing, t he D-1-receptor antagonist SCH23390 but not D-2 antagonist raclopride inhibited locomotion and rearing stimulated by cocaine (20 mg/kg). All behavioral responses of cocaine were abolished with increasing doses of raclopride and SCH23390. Sulpiride, a D-2 antagonist, exerted a bip hasic effect on locomotor activity (i.e., a low dose of sulpiride incr eased and a high dose decreased cocaine-induced locomotor activity). S ulpiride enhanced head circling, body shaking, and increases of rearin g induced by cocaine. D-2-receptor agonists quinpirole and bromocripti ne inhibited these responses, presumably by activating the typical ste reotyped behaviors such as sniffing at low doses, and licking and gnaw ing at high doses. The lowest dose of bromocriptine inhibited all beha viors induced by cocaine without producing typical stereotyped behavio rs in itself. SK&F38393, a D-1-receptor agonist, in combination with c ocaine did not induce typical stereotypy, which results in a synergist ic effect of D-1 and D-2-receptor activities. The increases of locomot ion and rearing, head circling, and body shaking induced by cocaine ma y involve the indirect activation of postsynaptic D-1 and D-2 receptor s, presumably via dopamine release, resulting from inhibition of the p resynaptic D-2 receptors. These results also provide evidence that the indirect stimulation of postsynaptic D-2 receptors by cocaine (20 mg/ kg) is insufficient to induce stereotyped behaviors, and that the role of dopamine D-1 receptors in mediating the behavioral actions of acut e cocaine appears to be more important than that of D-2 receptors. Our results also suggest that bromocriptine may be useful for the treatme nt of acute cocaine poisoning.