Positive and negative interactions in the behavioural expression of D1 and D2 receptor stimulation in a model of Parkinsonism: role of priming.
Previous exposure to a dopaminergic agonist (priming) strongly potentiates contralateral turning behaviour in response to D1 and D2 agonists in unilaterally 6-hydroxydopamine-lesioned rats. In order to study the influence of priming on the behavioural interaction of D1 and D2 receptors, we examined the effect of selective D1 and D2 receptor blockade on the contralateral turning induced by the mixed D2/D2 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 D1 (SCH 23390) or D2 (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 D1 receptor blockade and completely abolished by D2 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 D1 or D2 receptors abolished the second peak of rotation but, while D1 blockade reduced the total number of turns, D2 blockade failed to do so. Quantitative analysis of the interaction between D1 and D2 receptors in the overall turning effect, as well as in the time-course of turning behaviour, indicates that D1 and D2 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.
Morelli
M
M
Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Italy.
Fenu
S
S
Cozzolino
A
A
Di Chiara
G
G
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine; D010300:Parkinson Disease / Q000503:physiopathology*; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects
D001552:Benzazepines; D018492:Dopamine Antagonists; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; D016627:Oxidopamine; D001058:Apomorphine