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

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Abstract

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-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.

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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.

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Authors and Affiliations

  1. Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 814-0180, Fukuoka, Japan

    Nobuaki Egashira, Kenichi Mishima, Tomoko Uchida, Nobuyoshi Hasebe, Ai Mizuki, Katsunori Iwasaki & Michihiro Fujiwara

  2. Department of Psychiatry, Fukuoka University School of Medicine, 814-0180, Fukuoka, Japan

    Hiroshi Nagai, Hisanori Ishii & Ryoji Nishimura

  3. Department of Medicinal Resources Regulation, Graduate School of Pharmaceutical Sciences, Kyushu University, 812-8582, Japan

    Yukihiro Shoyama

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  1. Nobuaki Egashira
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  2. Kenichi Mishima
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Correspondence to Michihiro Fujiwara.

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Egashira, N., Mishima, K., Uchida, T. et al. Anandamide inhibits the DOI-induced head-twitch response in mice. Psychopharmacology 171, 382–389 (2004). https://doi.org/10.1007/s00213-003-1611-y

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