Effect of morphine-induced antinociception is altered by AF64A-induced lesions on cholinergic neurons in rat nucleus raphe magnus.
OBJECTIVE
To examine the role of cholinergic neurons in the nucleus raphe magnus (NRM) in noxious heat stimulation and in the effects of morphine-induced antinociception by rats.


METHODS
After the cholinergic neuron selective toxin, AF64A, was microinjected into the NRM, we examined changes in the antinociceptive threshold and effects of morphine (5 mg/kg, ip) using the hot-plate (HP) and tail-flick (TF) tests.


RESULTS
Systemic administration of morphine inhibited HP and TF responses in control rats. Microinjection of AF64A (2 nmol/site) into the NRM significantly decreased the threshold of HP response after 14 d, whereas the TF response was not affected. Morphine-induced antinociception was significantly attenuated in rats administered AF64A. Extracellular acetylcholine was attenuated after 14 d to below detectable levels in rats given AF64A. Naloxone (1 microg/site) microinjected into control rat NRM also antagonized the antinociceptive effect of systemic morphine.


CONCLUSIONS
These findings suggest that cholinergic neuron activation in the NRM modulates the antinociceptive effect of morphine simultaneously with the opiate system.
Abe
Kenji
K
Department of Neuroscience, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-8543, Japan.
Ishida
Kota
K
Kato
Masatoshi
M
Shigenaga
Toshiro
T
Taguchi
Kyoji
K
Miyatake
Tadashi
T
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000188:drug therapy; D017288:Pain Threshold / Q000187:drug effects*; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001388:Aziridines; D009466:Neuromuscular Blocking Agents; D009020:Morphine; C044894:ethylcholine aziridinium; D002794:Choline; D000109:Acetylcholine