title: Role of endocannabinoid and glutamatergic systems in DOI-induced head-twitch response in mice.
abstract: We previously reported that systemic administration of the endocannabinoid anandamide inhibited the head-twitches induced by the hallucinogenic drug 2,5-dimethoxy-4-iodoamphetamine (DOI) in mice, which is mediated via the activation of 5-HT(2A) receptors. Endocannabinoid and glutamatergic systems have been suggested to modulate the function of 5-HT(2A) receptors. In the present study, we further investigated the role of endocannabinoid and glutamatergic systems in DOI-induced head-twitch response in mice. An anandamide transport inhibitor AM404 (0.3-3mg/kg, i.p.), a fatty acid amide hydrolase inhibitor URB597 (0.1-10mg/kg, i.p.), a glutamate release inhibitor riluzole (0.3 and 1mg/kg, i.p.), a natural glutamate analog l-glutamylethylamide (theanine, 1 and 3mg/kg, p.o.) and an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist NBQX (0.01-0.3mg/kg, i.p.) significantly inhibited DOI-induced head-twitch response. The AMPA receptor positive modulator aniracetam (30 or 100mg/kg, p.o.) reversed inhibition of head-twitch response by NBQX and URB597. These findings indicated that endocannabinoid and glutamatergic systems participate in the mechanism of action of DOI to induce head-twitch response.
authors.affiliation: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan. n-egashi@pharm.med.kyushu-u.ac.jp
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Atsunori
authors.initials: A
authors.lastname: Shirakawa
authors.forename: Ryoko
authors.initials: R
authors.lastname: Okuno
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Ryozo
authors.initials: R
authors.lastname: Oishi
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D000662:Amphetamines / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology* / Q000502:physiology*; D063388:Endocannabinoids; D018698:Glutamic Acid / Q000031:analogs & derivatives / Q000502:physiology*; D019416:Head Movements / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice
chemical_list: D000662:Amphetamines; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; C041336:4-iodoamphetamine; D018698:Glutamic Acid