title: Effect of morphine-induced antinociception is altered by AF64A-induced lesions on cholinergic neurons in rat nucleus raphe magnus.
abstract: 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.
authors.affiliation: Department of Neuroscience, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
authors.forename: Kota
authors.initials: K
authors.lastname: Ishida
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kato
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shigenaga
authors.forename: Kyoji
authors.initials: K
authors.lastname: Taguchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Miyatake
mesh_terms: 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
chemical_list: D001388:Aziridines; D009466:Neuromuscular Blocking Agents; D009020:Morphine; C044894:ethylcholine aziridinium; D002794:Choline; D000109:Acetylcholine