Synergistic interaction between dopamine D-1 and D-2 receptor agonists: circling behaviour of rats with hemitransection.
Circling behaviour induced by dopamine (DA) agonists with different D-1/D-2 receptor selectivity was studied in rats with hemitransection at a level caudal to the striatum. The mixed D-1/D-2 agonist apomorphine induced ipsilateral circling behaviour after administration of doses similar to those that induced stereotyped behaviour in unlesioned rats. The effect of apomorphine was not influenced by co-treatment with SK & F 38393 or quinpirole, indicating that apomorphine induces a comparable D-1 and D-2 receptor stimulation in vivo also. Three selective D-1 agonists, SK & F 38393, SK & F 75670 and Lu 24-040 had no effects alone, while the preferential D-2 agonists quinpirole, pergolide and (-)-N-propylnorapomorphine induced ipsilateral circling of weaker intensity than did apomorphine. After co-treatment with SK & F 38393 the effects of these compounds were markedly increased. Combination of SK & F 38393, SK & F 75670 or Lu 24-040 with quinpirole induced circling with intensities similar to those seen after apomorphine. Pretreatment with the D-1 antagonist SCH 23390 or the D-2 antagonist YM 09151-2 completely antagonized the ipsilateral circling induced by either apomorphine or quinpirole + SK & F 38393. A range of partial (autoreceptor) D-2 agonists, i.e. (-)-3-PPP, (+)-3-phenethyl-PP, terguride, EMD 23448 and B-HT 920 were all ineffective as was the alpha 2-adrenoceptor agonist clonidine. However, B-HT 920 induced strong ipsilateral circling after combination with SK & F 38393, whereas (-)-3-PPP was ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D004357:Drug Synergism; D004873:Ergolines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011954:Receptors, Dopamine / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects*
D001552:Benzazepines; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001058:Apomorphine