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

Nobuaki Egashira, Kenichi Mishima, Tomoko Uchida, Nobuyoshi Hasebe, Hiroshi Nagai, Ai Mizuki, Katsunori Iwasaki, Hisanori Ishii, Ryoji Nishimura, Yukihiro Shoyama, Michihiro Fujiwara

Research output: Contribution to journalArticle

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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-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.

Original languageEnglish
Pages (from-to)382-389
Number of pages8
JournalPsychopharmacology
Volume171
Issue number4
DOIs
Publication statusPublished - Feb 1 2004
Externally publishedYes

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Dronabinol
Head
rimonabant
Receptor, Serotonin, 5-HT2A
Cyclooxygenase Inhibitors
Artificial Receptors
Receptor, Serotonin, 5-HT2C
Cannabinoid Receptor Agonists
anandamide
Cannabinoid Receptor CB1
Endocannabinoids
Propane
Cannabinoids
Cannabis
Arachidonic Acid
Indomethacin
Aspirin
Injections

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Egashira, N., Mishima, K., Uchida, T., Hasebe, N., Nagai, H., Mizuki, A., ... Fujiwara, M. (2004). Anandamide inhibits the DOI-induced head-twitch response in mice. Psychopharmacology, 171(4), 382-389. https://doi.org/10.1007/s00213-003-1611-y

Anandamide inhibits the DOI-induced head-twitch response in mice. / Egashira, Nobuaki; Mishima, Kenichi; Uchida, Tomoko; Hasebe, Nobuyoshi; Nagai, Hiroshi; Mizuki, Ai; Iwasaki, Katsunori; Ishii, Hisanori; Nishimura, Ryoji; Shoyama, Yukihiro; Fujiwara, Michihiro.

In: Psychopharmacology, Vol. 171, No. 4, 01.02.2004, p. 382-389.

Research output: Contribution to journalArticle

Egashira, N, Mishima, K, Uchida, T, Hasebe, N, Nagai, H, Mizuki, A, Iwasaki, K, Ishii, H, Nishimura, R, Shoyama, Y & Fujiwara, M 2004, 'Anandamide inhibits the DOI-induced head-twitch response in mice', Psychopharmacology, vol. 171, no. 4, pp. 382-389. https://doi.org/10.1007/s00213-003-1611-y
Egashira N, Mishima K, Uchida T, Hasebe N, Nagai H, Mizuki A et al. Anandamide inhibits the DOI-induced head-twitch response in mice. Psychopharmacology. 2004 Feb 1;171(4):382-389. https://doi.org/10.1007/s00213-003-1611-y
Egashira, Nobuaki ; Mishima, Kenichi ; Uchida, Tomoko ; Hasebe, Nobuyoshi ; Nagai, Hiroshi ; Mizuki, Ai ; Iwasaki, Katsunori ; Ishii, Hisanori ; Nishimura, Ryoji ; Shoyama, Yukihiro ; Fujiwara, Michihiro. / Anandamide inhibits the DOI-induced head-twitch response in mice. In: Psychopharmacology. 2004 ; Vol. 171, No. 4. pp. 382-389.
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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-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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AU - Nagai, Hiroshi

AU - Mizuki, Ai

AU - Iwasaki, Katsunori

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