The role of dopaminergic mechanisms in mediating the central behavioral effects of morphine in rodents.
Morphine has been universally assumed to act solely on opiate receptors, and predominantly on mu receptors. In consonance with this, several studies have demonstrated that opiate mu agonists and dopaminergic agonists and antagonists are incapable of binding each other's receptors, except at extremely high concentrations (nor, for that matter, are acetylcholine, serotonin, gamma-hydroxybutyrate, norepinephrine or histamine able to bind opiate receptors). Yet, while other neurotransmitter antagonists (e.g. alpha- and beta-adrenoceptor-blocking agents) are for the most part limited in their effect on opiate-induced responses, many of the central effects elicited by morphine and other opioids have been found to be markedly potentiated by dopamine (DA) antagonists and reversed by direct and indirect DA agonists. Even more significantly, DA antagonists (especially those appreciably inhibiting DA release selectively) can also mimic many of these effects in low to moderate doses. Since DA antagonists do not act by binding opiate receptors, it is quite likely that morphine and other opiate mu receptor agonists may at least partially induce many of their acute central effects by means of an inhibition of postsynaptic DA receptor arousal. This appears to be a consequence of morphine binding its own (mu) receptors localized on central DA nerve terminals, resulting in an alteration of presynaptic DA release. This review does not exclude the important role of other neurotransmitter substances in the action of morphine, but rather emphasizes, and limits itself to considering, the importance of the role of dopamine in morphine-induced behaviors.
D000374:Aggression / Q000187:drug effects; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu; D013239:Stereotyped Behavior / Q000187:drug effects
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine; D004298:Dopamine