TY - JOUR
T1 - Anandamide inhibits the DOI-induced head-twitch response in mice
AU - Egashira, Nobuaki
AU - Mishima, Kenichi
AU - Uchida, Tomoko
AU - Hasebe, Nobuyoshi
AU - Nagai, Hiroshi
AU - Mizuki, Ai
AU - Iwasaki, Katsunori
AU - Ishii, Hisanori
AU - Nishimura, Ryoji
AU - Shoyama, Yukihiro
AU - Fujiwara, Michihiro
N1 - Funding Information:
Acknowledgements Part of this study was supported by a Grant-in-Aid for Scientific Research (No. 12771472) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by Research Grants (10A-3 and 13A-3) for Nervous and Mental Disorders from the Ministry of Health and Welfare.
PY - 2004/2
Y1 - 2004/2
N2 - Rationale: Recently, Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, and synthetic cannabinoid receptor agonists reportedly reduced the head-twitches induced by the 5-HT 2A/2C receptor agonist 1-(2,5-dimethoxy 4-iodophenyl)-2-amino propane (DOI) in mice, which is mediated via the activation of 5-HT 2A receptor. However, the effect of endogenous cannabinoid anandamide on the head-twitch response has not been studied. Objectives: In this study, we investigated the effect of anandamide on the DOI-induced head-twitch response in mice. Methods: Five minutes after the injection of DOI (5 mg/kg IP), the number of head-twitches was counted for a 5-min period. THC or anandamide was injected IP 60 min or 10 min before the number of head-twitches was counted, respectively. Results: THC and anandamide each reduced the DOI-induced head-twitch response. The inhibition of the DOI-induced head-twitch response by THC was reversed by SR141716A (N-piperidino-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide), a CB 1 receptor antagonist, while the effect of anandamide was not blocked by SR141716A. Cyclooxygenase (COX) inhibitors such as aspirin and indomethacin reversed the inhibition of the DOI-induced head-twitch response by anandamide. On the other hand, COX inhibitors did not affect the inhibition of the DOI-induced head-twitch response by THC. Conclusions: Taken together, these findings suggest that the endocannabinoid anandamide may inhibit 5-HT 2A receptor-mediated function via the arachidonic acid cascade, but not via a direct interaction with the CB1 cannabinoid receptor, and that the mechanism of its action is clearly different from that of THC.
AB - Rationale: Recently, Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, and synthetic cannabinoid receptor agonists reportedly reduced the head-twitches induced by the 5-HT 2A/2C receptor agonist 1-(2,5-dimethoxy 4-iodophenyl)-2-amino propane (DOI) in mice, which is mediated via the activation of 5-HT 2A receptor. However, the effect of endogenous cannabinoid anandamide on the head-twitch response has not been studied. Objectives: In this study, we investigated the effect of anandamide on the DOI-induced head-twitch response in mice. Methods: Five minutes after the injection of DOI (5 mg/kg IP), the number of head-twitches was counted for a 5-min period. THC or anandamide was injected IP 60 min or 10 min before the number of head-twitches was counted, respectively. Results: THC and anandamide each reduced the DOI-induced head-twitch response. The inhibition of the DOI-induced head-twitch response by THC was reversed by SR141716A (N-piperidino-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide), a CB 1 receptor antagonist, while the effect of anandamide was not blocked by SR141716A. Cyclooxygenase (COX) inhibitors such as aspirin and indomethacin reversed the inhibition of the DOI-induced head-twitch response by anandamide. On the other hand, COX inhibitors did not affect the inhibition of the DOI-induced head-twitch response by THC. Conclusions: Taken together, these findings suggest that the endocannabinoid anandamide may inhibit 5-HT 2A receptor-mediated function via the arachidonic acid cascade, but not via a direct interaction with the CB1 cannabinoid receptor, and that the mechanism of its action is clearly different from that of THC.
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U2 - 10.1007/s00213-003-1611-y
DO - 10.1007/s00213-003-1611-y
M3 - Article
C2 - 14586538
AN - SCOPUS:10744232611
VL - 171
SP - 382
EP - 389
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 4
ER -