Anandamide inhibits the DOI-induced head-twitch response in mice

被引:22
作者
Egashira, N
Mishima, K
Uchida, T
Hasebe, N
Nagai, H
Mizuki, A
Iwasaki, K
Ishii, H
Nishimura, R
Shoyama, Y
Fujiwara, M [1 ]
机构
[1] Fukuoka Univ, Fac Pharmaceut Sci, Dept Neuropharmacol, Fukuoka 8140180, Japan
[2] Fukuoka Univ, Sch Med, Dept Psychiat, Fukuoka 8140180, Japan
[3] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Med Resources Regulat, Fukuoka 8128582, Japan
关键词
head-twitch response; 5-HT; receptor; cyclooxygenase inhibitor; anandamide; Delta(9)-tetrahydrocannabinol; CB; cannabinoid receptor; VR; vanilloid receptor;
D O I
10.1007/s00213-003-1611-y
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Rationale. Recently, Delta(9)-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, and synthetic cannabinoid receptor agonists reportedly reduced the head-twitches induced by the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy 4-iodophenyl)-2-amino propane (DOI) in mice, which is mediated via the activation of 5-HT2A 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 CB1 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-HT2A 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.
引用
收藏
页码:382 / 389
页数:8
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