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

The effects of morphine and haloperidol were compared on dopamine-sensitive adenylate cyclase activity of the rat caudate nucleus, an enzyme activity which has been related to the “dopamine receptor.” The response of adenylate cyclase activity to dopamine was measured in a hypo-osmotically shocked mitochondrial-synaptosomal fraction. The addition of 3–300 μM morphine, levorphanol, dextrorphan, d- and l-methadone, nalorphine and naloxone in vitro caused no significant changes in the response to dopamine, while addition of haloperidol in vitro completely inhibited the dopamine response at a concentration of 3 μM or higher. When morphine was administered subcutaneously at a dose of 60 mg/kg, significant increases were found in basal and dopamine-sensitive adenylate cyclase activity from the rat caudate from 15 to 120 min after the injection. Twenty to sixty min after the subcutaneous injection of 20 mg/kg of haloperidol, 1.7 to 2.0-fold increases were found in the dopamine-stimulated activity. The increased dopamine-sensitive cyclase activity found after acute administration of haloperidol o r morphine returned to control values 4 hr after the injection. Implantation of two morphine pellets for 2 or 3 days produced a significant increase in the dopamine sensitivity of the cyclase activity without altering basal activity. These results from experiments in vitro and in vivo suggest that, while haloperidol has a direct effect on the dopamine receptor-associated cyclase activity, morphine must act by another mechanism, and that chronic use of either drug produces enhanced dopamine sensitivity.