Differential ability of selective and non-selective dopamine agonists to induce climbing in the rat indicates the involvement of both D-1 and D-2 receptors in this behaviour.
Approximately 50% of female Wistar rats examined exhibited a continuous climbing response to a screening dose of apomorphine. In animals identified as climbing, the mixed D-1/D-2 agonists apomorphine, pergolide and L-dopa, and the indirectly acting agonists nomifensine and (+)-amphetamine, induced a dose-related climbing response. The selective D-1 agonist SKF 38393 caused only minimal climbing, and the selective D-2 agonists bromocriptine, lisuride and LY 141865 induced a weak climbing response. All agonists examined, except SKF 38393, caused a dose-related stereotypy response. The selective D-1 antagonist SCH 23390, and the selective D-2 antagonist sulpiride, both produced maximum inhibition of apomorphine-induced climbing. SCH 23390 also inhibited stereotyped behaviour, but sulpiride was less effective. In animals identified as "non-climbers" using the screening dose of apomorphine, only L-dopa induced a marked climbing response. Nomifensine and bromocriptine produced weak or discontinuous climbing in this group, while the other agonists examined had little or no effect. In contrast all drugs examined, except SKF 38393, induced stereotyped behaviour of the same intensity observed in the "climbers". It is concluded that stimulation of both D-1 and D-2 receptors is necessary to induce a continuous climbing behaviour in rats. D-2, but not D-1 stimulation, alone can induce a weak or discontinuous climbing response, but concomitant stimulation of D-1 receptors potentiates this effect. Failure of some rats to climb does not appear to be related to relative degrees of D-1 and D-2 stimulation.
Davis
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A
MRC Movement Disorders Research Group, University Department of Neurology, London, UK.
Jenner
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P
Marsden
C D
CD
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D007980:Levodopa / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D010479:Pergolide / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D010479:Pergolide; D001971:Bromocriptine; D007980:Levodopa; D013469:Sulpiride; D000661:Amphetamine; D003000:Clonidine; D001058:Apomorphine