Behavioural pharmacology of 'D-1-like' dopamine receptors: further subtyping, new pharmacological probes and interactions with 'D-2-like' receptors.

1. D-1 receptors are now recognised to play a critical psychopharmacological role in the regulation of unconditioned motor and numerous other aspects of behaviour. 2. There appears to exist a broad family of 'D-1-like' receptors in terms both of differential coupling to distinct messenger/transduction mechanisms and of gene cloning, whose behavioural roles remain to be clarified. 3. The adenylyl cyclase-inhibiting benzazepine SK&F 83959 induces behavioural responses in rats that are similar to those induced by the full efficacy cyclase-stimulating isochroman A 68930 but not to those induced by its high efficacy partial agonist benzazepine congener R-6-Br-APB; these data indicate roles for individual 'D-1-like' receptors in mediating distinct elements of dopaminergic behaviour. 4. The putative D-1 autoreceptor agonist B-HT 920 and the putative D-3 agonist 7-OH-DPAT demonstrate different behavioural profiles when given both alone and in combination with the selective 'D-1-like' antagonist BW 737C; D-3 receptors may participate in cooperative/synergistic but not in oppositional 'D-1-like': 'D-2-like' interactions. 5. Such interactions apparent at the level of behaviour are complemented by evidence for similar interactions at numerous alternative levels of function, though these may differ between rodent and primate species. 6. A broader range of more selective agonists and antagonists, able to distinguish between individual members of the 'D-1-like' and of the 'D-2-like' receptor families are needed to clarify these issues.

Grooming and vacuous chewing induced by SK&F 83959, an agonist of dopamine 'D1-like' receptors that inhibits dopamine-sensitive adenylyl cyclase.

The benzazepine SK&F 83959 demonstrates high affinity for dopamine D1 receptors and potently inhibits the stimulation of adenylyl cyclase by dopamine. This compound induced the same intense grooming behaviour identified previously as a characteristic response to typical dopamine D1 receptor agonists such as SK&F 77434 that stimulate adenylyl cyclase; it also induced vacuous chewing. These findings constitute direct evidence for a behaviourally relevant subtype of 'D1-like' receptor that is not linked to adenylyl cyclase.