Dopamine-sensitive adenylate cyclase of the caudate nucleus of rats treated with morphine

Abstract

The addition of narcotic analgesics in vitro to nerve ending preparations from rat caudate nucleus in an assay of adenylate cyclase activity (AC) resulted in an inhibition of basal AC only at drug concentrations of 10− 4M or higher, and no inhibition of dopamine-stimulated (DA) AC at these drug concentrations. The acute administration of morphine at a moderately high dose (60 mg/kg) produced an increase in striatal cAMP levels, and increases in basal and DA-AC in caudate nerve-endings. In morphine-tolerant rats, striatal cAMP levels and basal AC were similar to control values, while DA-AC was elevated. These results suggest: (1) that opiates do not act directly on DA-AC, the ‘dopamine receptor’, and (2) that the observed behavioural DA sensitivity in tolerant animals may be produced by the DA-AC supersensitivity.