title: Dopamine D2-like receptor in the nucleus accumbens is involved in the antinociceptive effect of nitrous oxide.
abstract: BACKGROUND
  The mechanism of the antinociceptive effects of nitrous oxide (N(2)O) has not been completely elucidated. On the other hand, numerous studies have indicated that mesolimbic dopaminergic neurons, which are thought to be involved in rewarding and reinforcement processes, play important roles in the supraspinal pain-suppression system. We hypothesized that the mesolimbic dopaminergic system is involved in the antinociceptive effect of N(2)O.
  
  
  METHODS
  Adult male Fischer rats were used in this study. To examine whether the dopaminergic system is activated by N(2)O, frozen sections of the ventral tegmental area of rats exposed to 75% N(2)O were double-stained for c-Fos and tyrosine hydroxylase. To clarify whether the dopaminergic system is involved in the antinociceptive action of N(2)O, saline or raclopride, a dopamine D(2)-like receptor antagonist, was injected into the nucleus accumbens (NAc) shell region. After exposure to 25% oxygen-75% nitrogen or 25% oxygen-75% N(2)O for 30 min, rats were subjected to formalin test, and the spinal cord was examined immunohistochemically.
  
  
  RESULTS
  Exposure to 75% N(2)O increased c-Fos expression in tyrosine hydroxylase-positive cells in the ventral tegmental area. Raclopride, injected into the NAc shell region, attenuated the antinociceptive effect of N(2)O in the formalin test, and blocked the suppressive effect of N(2)O on the formalin-induced c-Fos expression in the dorsal horn of the spinal cord by N(2)O.
  
  
  CONCLUSIONS
  It is possible that inhalation of N(2)O activates mesolimbic dopaminergic neurons, and that the antinociceptive effect of N(2)O is at least partially mediated by dopamine D(2)-like receptors in the NAc shell region.
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. sahoko@kuhp.kyoto-u.ac.jp
authors.forename: Sahoko
authors.initials: S
authors.lastname: Koyanagi
authors.forename: Shugaku
authors.initials: S
authors.lastname: Himukashi
authors.forename: Kumiko
authors.initials: K
authors.lastname: Mukaida
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shichino
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000008:administration & dosage; D005557:Formaldehyde; D008297:Male; D008845:Microinjections; D009609:Nitrous Oxide / Q000494:pharmacology* / Q000627:therapeutic use; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010147:Pain Measurement; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020891:Raclopride / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D000700:Analgesics; D018492:Dopamine Antagonists; D016760:Proto-Oncogene Proteins c-fos; D017448:Receptors, Dopamine D2; D005557:Formaldehyde; D020891:Raclopride; D014446:Tyrosine 3-Monooxygenase; D009609:Nitrous Oxide