Actions of dopaminergic drugs on dopamine stimulated adenosine 3',5' monophosphate production in rat neostriatum and limbic forebrain

There is a good agreement between the structure activity requirements for stimulation of cyclic AMP production in striatal homogenates and the results obtained in other test systems for dopamine receptor agonists, such as the renal artery (Goldberg et al., 1968) and in snail neurons (Woodruff and Walker, 1969). There is also good agreement between the biochemical findings and the behavioural activity of some of the compounds tested. For example, the behavioural effects of apomorphine, 2 amino 6,7 dihydroxy 1,2,3,4 tetrahydronaphthalene and 2 amino 1,2,3,4 tetrahydronaphthalene are consistent with the view that these compounds are dopaminergic agonists. Taken together with previous findings that the dopamine sensitive adenylate cyclase is not stimulated by β adrenoceptor agonists such as isoprenaline and is only weakly stimulated by noradrenaline, and that the system is sensitive to antagonism by neuroleptic drugs but less so by traditional α adrenoceptor antagonists and not at all by β adrenoceptor antagonists, these findings provide good grounds for retaining the notion that the dopamine sensitive adenylate cyclase represents a biochemical manifestation of CNS dopamine receptor activation. This does not, of course, mean that the adenylate cyclase is necessarily the CNS dopamine receptor, since as with other hormonal transmitter sensitive adenylate cyclase mechanisms a primary receptor molecule (which may constitute a regulatory subunit of the adenylate cyclase complex) may well be interposed between the site of dopamine action and the stimulation of cyclase activity.