Original Article

Effect of morphine-induced antinociception is altered by AF64A-induced lesions on cholinergic neurons in rat nucleus raphe magnus.

Kenji ABE, Kota ISHIDA, Masatoshi KATO, Toshiro SHIGENAGA, Kyoji TAGUCHI, Tadashi MIYATAKE


AIM: 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.
CONCLUSION: These findings suggest that cholinergic neuron activation in the NRM
modulates the antinociceptive effect of morphine simultaneously with the opiate

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