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.
Egashira
Nobuaki
N
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 814-0180 Fukuoka, Japan.
Mishima
Kenichi
K
Uchida
Tomoko
T
Hasebe
Nobuyoshi
N
Nagai
Hiroshi
H
Mizuki
Ai
A
Iwasaki
Katsunori
K
Ishii
Hisanori
H
Nishimura
Ryoji
R
Shoyama
Yukihiro
Y
Fujiwara
Michihiro
M
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