Interactions of Central Transmitter-Substances with Narcotic and Narcotic-Antagonist Analgesics

Abstract

Using the technique of intracerebroventricular (i.c.v.) microinjection in conscious mice and rats, the possible involvement of putative central nervous system transmitter-substances in the anti-nociceptive effects of morphine and the narcotic-antagonist analgesics nalorphine and pentazocine has been investigated. A number of nociceptive test procedures has been utilised, in an attempt to counter the deficiencies of any one test. The results obtained provide strong evidence in favour of a central cholinergic system being involved in the production of the anti-nociceptive effects of morphine in both the mouse and the rat. Evidence is also presented which suggests that activity in a system involving 5-hydroxytryptamine in the brain is important in bringing about the anti-nociceptive action of morphine, and that of the cholinomimetic agent oxotremorine. The catecholamines, dopamine and noradrenaline, would appear to have opposing functions with regard to the activity of morphine. Injections of dopamine i.c.v. enhance the anti-nociceptive properties of morphine, whilst injections of noradrenaline i.c.v. strongly antagonise morphine's action. The picture with regard to the narcotic-antagonist analgesics is less clear, partly because of the inadequacies of the test methods available, and partly because the two agents chosen in this group (nalorphine and pentazocine) appear to possess quite different spectra of pharmacological activity, despite being classified in the same group. Thus pentazocine resembles morphine in that it is antagonised by naloxone, whereas nalorphine is not, whilst on the other hand nalorphine appears to resemble morphine more than does pentazocine with regard to its interactions with central transmitters. Thus nalorphine would appear to involve a central cholinergic system, whilst this is untrue of pentazocine. The results presented are discussed in the light of the current status of acetylcholine, 5-hydroxytryptamine, noradrenaline and dopamine as neurohumoral agents in the central nervous system.