Interactions of morphine with putative neurotransmitters in the mesencephalic reticular formation.
Acetylcholine (ACh) and norepinephrine (NE) have been identified previously as putative nociceptive neurotransmitters in the mesencephalic reticular formation (MRF) of the rat because they frequently mimic the change in neuronal firing (usually an increase) evoked by a noxious stimulus (NS). The purpose of this study was to determine if 1.) morphine (M) acts to prevent the increase in firing evoked by a NS by blocking the effects of either of these two neurotransmitters and 2.) if this effect is a specific narcotic effect. Using the technique of microiontophoresis in conjunction with extracellular recording, we located single units in the MRF in which 1.) neuronal firing was accelerated by a NS: 2.) M blocked this response; and 3.) either ACh or NE mimicked the effect of the NS. Neurons meeting these three criteria were studied further to determine if morphine would also block the response to either of the neurotransmitters and if this was a specific narcotic effect. We found that morphine blocked the increase in neuronal firing evoked by the NS and ACh or the NS and NE in over 50% of the cells meeting the above criteria. Some neurons were found in which both ACh and NE mimicked the NS and M blocked all three responses. This blockade of these neurotransmitters was a specific narcotic effect because it could be reversed by the systemic administration of naloxone. These data lead to the tentative hypothesis that M, acting via an opiate receptor, blocks the increase in neuronal firing evoked by a NS by blocking the postsynaptic effects of either ACh or NE. This may be one of the mechanisms by which morphine acts to produce analgesia.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D007478:Iontophoresis / Q000379:methods; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012154:Reticular Formation / Q000187:drug effects* / Q000502:physiology
D009270:Naloxone; D009020:Morphine; D000109:Acetylcholine; D009638:Norepinephrine