AbstractUsing 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.
|Date of Award||1972|
- central transmitter-substances
- narcotic analgesics
- narcotic-antagonist analgesics