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Pharmacological characterization in the rat of grooming and other behavioural responses to the D1 dopamine receptor agonist R-SK&F 38393

Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St Stephen's Green, Dublin 2, Ireland

John L. Waddington

Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St Stephen's Green, Dublin 2, Ireland

Grooming, sniffing, Iocomotor and rearing responses to the D₁ dopamine receptor agonist SK&F 38393, as the racemic compound or its R-enantiomer, were characterized pharmacologically using typical neuroleptics, non-dopaminergic antagonists, selective D₁ antagonists and selective D₂ antagonists. The typical neuroleptics haloperidol and flupenthixol blocked all behaviours induced by SK&F 38393; this action of flupenthixol was stereoselective for its cis(Z)-isomer but not its trans(E)-isomer. Non-dopaminergic antagonists failed to reproduce the consistent effects of typical neuroleptics. The selective D₁ antagonist SCH 23390 potently blocked all responses to SK&F 38393. A related selective D₁ antagonist, SK&F 83566, also blocked these responses, and this action was stereoselective for its R-enantiomer but not its S-enantiomer. These data suggest that D₁ receptor stimulation is the primary mechanism underlaying the induction of these behaviours by SK&F 38393. However, the expression of certain individual responses to SK&F 38393 were sensitive to attenuation by the selective D₂ antagonists sulpiride or metoclopramide. These results extend the emerging view that the D₁ receptor is behaviourally relevant and that there exist functional interactions between D₁ and D₂ receptor systems in the regulation of behaviour.

Journal of Psychopharmacology, Vol. 1, No. 3, 177-183 (1987)
DOI: 10.1177/026988118700100304


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