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


OBJECTIVE
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 CB(1) cannabinoid receptor, and that the mechanism of its action is clearly different from that of THC.
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 814-0180 Fukuoka, Japan.
Nobuaki
N
Egashira
Kenichi
K
Mishima
Tomoko
T
Uchida
Nobuyoshi
N
Hasebe
Hiroshi
H
Nagai
Ai
A
Mizuki
Katsunori
K
Iwasaki
Hisanori
H
Ishii
Ryoji
R
Nishimura
Yukihiro
Y
Shoyama
Michihiro
M
Fujiwara
D000662:Amphetamines / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D019416:Head Movements / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D053284:Polyunsaturated Alkamides
D000662:Amphetamines; D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C078814:anandamide