D-1 dopamine receptors and the topography of unconditioned motor behaviour: studies with the selective,'full efficacy' benzazepine D-1 agonist SKF 83189

Abstract

Approaches to studying the role of the D-1 receptor in the regulation of unconditioned motor behaviour, and the current status of results derived therefrom, are reviewed; the desirability of utilizing drug tools other than the benzazepine partial D-1 agonist SKF 38393 is emphasized, particularly the need for studies with full D-1 agonists. Behavioural responses to the benzazepine putative full D-1 agonist SKF 83189 were compared with those to its high potency but only partial agonist counterpart SKF 77434. Both agents produced qualitatively and generally quantitatively similar behavioural responses, particularly intense grooming in the absence of vacuous chewing; thus, their behavioural properties appeared entirely unrelated to their efficacies to stimulate adenylate cyclase, the classical definition of a D-1 agonist. There may be complex interactions between selectivity, intrinsic activity and CNS penetrability, or a high D-1 receptor reserve ('spare' receptors); however, these results point towards the notion of behaviourally relevant subtypes of D-1 receptor, possibly utilizing transduction mechanisms other than, or additional to, adenylyl cyclase, for which there is emerging evidence.