Dopamine D2-like receptor in the nucleus accumbens is involved in the antinociceptive effect of nitrous oxide.
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.
Koyanagi
Sahoko
S
Department of Anesthesia, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. sahoko@kuhp.kyoto-u.ac.jp
Himukashi
Shugaku
S
Mukaida
Kumiko
K
Shichino
Tsutomu
T
Fukuda
Kazuhiko
K
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
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