Positive and negative interactions in the behavioural expression of d 1 and D 2 receptor stimulation in a model of parkinsonism: Role of priming

Abstract

Previous exposure to a dopaminergic agonist (priming) strongly potentiates contralateral turning behaviour in response to D 1 and D 2 agonists in unilaterally 6-hydroxydopamine-lesioned rats. In order to study the influence of priming on the behavioural interaction of D 1 and D 2 receptors, we examined the effect of selective D 1 and D 2 receptor blockade on the contralateral turning induced by the mixed D 1 /D 2 agonist apomorphine in drug-naive and primed 6-hydroxydopamine-lesioned rats. In drug-naive rats, apomorphine induced a dose-related, apparently monophasic rotation curve. Administration of selective D 1 (SCH 23390) or D 2 (raclopride) antagonists abolished the contralateral turning induced by 0.1 mg/kg of apomorphine and partially inhibited that induced by 0.5 mg/kg. In primed rats low doses of apomorphine (0.05 mg/kg) induced an apparently monophasic contralateral turning which was reduced by D 1 receptor blockade and completely abolished by D 2 receptor blockade; a higher dose of apomorphine (0.1 mg/kg) instead elicited a biphasic (two-peak) pattern of rotation. After this dose of the agonist, blockade of D 1 or D 2 receptors abolished the second peak of rotation but, while D 1 blockade reduced the total number of turns, D 2 blockade failed to do so. Quantitative analysis of the interaction between D 1 and D 2 receptors in the overall turning effect, as well as in the time-course of turning behaviour, indicates that D 1 and D 2 receptors interact not only positively but also negatively. After higher doses of apomorphine, both negative and positive interactions take place sequentially during the time-course of apomorphine action and provide a clue for explaining the two-peak pattern of rotation observed after apomorphine in rats previously exposed to the drug.