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

Grooming, sniffing, Iocomotor and rearing responses to the D(1) dopamine receptor agonist SK&F 38393, as the racemic compound or its R-enantiomer, were characterized pharmacologically using typical neuroleptics, non-dopaminergic antagonists, selective D(1) antagonists and selective D(2) 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 D(1) antagonist SCH 23390 potently blocked all responses to SK&F 38393. A related selective D(1) 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 D(1) 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 D(2) antagonists sulpiride or metoclopramide. These results extend the emerging view that the D(1) receptor is behaviourally relevant and that there exist functional interactions between D(1) and D(2) receptor systems in the regulation of behaviour.