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

Abstract

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.