Dopamine-sensitive adenylate cyclase in homogenates of rat nucleus accumbens: structure-activity studies and effects of agonists and antagonists

A study has been made of the structural requirements for activity on the dopamine-sensitive adenylate cyclase present in homogenates of rat nucleus accumbens. The only active phenylethylamine derivatives tested were those containing hydroxy groups at the 3 and 4 positions on the benzene ring, a two carbon side chain and a terminal nitrogen, either unsubstituted or containing a single methyl group. The alpha- and beta-adrenergic agonists, phenylephrine and isoprenaline respectively, were both inactive. Norsalsolinol was a weak agonist producing only a 50% stimulation of adenylate cyclase activity. The typical neuroleptic drugs, fluphenazine and cis-flupenthixol were both potent antagonists of the dopamine response as opposed to the atypical neuroleptics, metoclopramide and sulpiride, and the alpha- and beta-adrenergic blocking agents, phentolamine and propranolol respectively, which were all inactive. Our results indicate that the dopamine receptors associated with adenylate cyclase in the nucleus accumbens are similar to those in the corpus striatum.