Behavioural pharmacology of 'D1-like' dopamine receptors: Further subtyping, new pharmacological probes and interactions with 'D-2-like' receptors

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 1995-01, Vol.19 (5), p.811-831
• Main Authors: Waddington, J L, Daly, SA, Downes, R P, Deveney, A M, McCauley, P G, O'Boyle, K M
• Format: Article
• Language: English
• ISSN: 0278-5846

D-1 receptors are now recognised to play a critical psychopharmacological role in the regulation of unconditioned motor and numerous other aspects of behaviour. 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. 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. 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. 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. 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.