Differential effects of dopamine D-1 and D-2 receptor agonists on eeg activity and behaviour in the rabbit

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SKF 38393, a selective agonist for dopamine D-1 receptors, LY 171555, a selective agonist for D-2 receptors and apomorphine, an agonist for both receptor sites, all induced activation of the electrical activity of the brain (EEG) in the rabbit. While SKF 38393 induced EEG changes without concomitant signs of stereotyped behaviour, the injection of both LY 171555 and apomorphine also elicited marked behavioural effects, mostly stereotyped mouth and head movements. The EEG effects of SKF 38393 were prevented by SCH 23390 (0.003 mg/kg i.V.), but not by (−)-sulpiride (6.2–25 mg/kg i.V.). Haloperidol attenuated the effects induced by SKF 38393 only at a dose (1 mg/kg) that induced EEG changes of its own. Similarly, effects of apomorphine on both EEG and behaviour were prevented by SCH 23390 and to a lesser extent by haloperidol, but not influenced by (−)-sulpiride. Different patterns of interactions were observed when D-2 receptors were selectively stimulated by LY 171555. Behavioural effects induced by LY 171555 were fully inhibited by both (−)-sulpiride (6.2–12.5 mg/kg i.v.) and haloperidol (0.1–0.3 mg/kg i.v.). The drug SCH 23390 attenuated some behavioural components at 0.3 mg/kg (i.v.), a dose at least 100-fold that effective on the EEG effects induced by SKF 38393. However, all these antagonists exerted weak or no effects on EEG activation induced by LY 171555 and did not restore the control patterns at any doses examined. These data indicate that the population of D-1 receptors is strongly involved in the regulation of EEG and behavioural arousal, while D-2 receptors appear to be mostly involved in mediating stereotyped movements. Based on the findings with apomorphine, it is also suggested that D-1 and D-2 receptors are functionally inter-related, with D-1 receptors playing a prominent role in the modulation of the EEG and in behavioural arousal.