Role of endocannabinoid and glutamatergic systems in DOI-induced head-twitch response in mice

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-HT2A receptors. Endocannabinoid and glutamatergic systems have...

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Veröffentlicht in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2011-07, Vol.99 (1), p.52-58
Hauptverfasser: Egashira, Nobuaki, Shirakawa, Atsunori, Okuno, Ryoko, Mishima, Kenichi, Iwasaki, Katsunori, Oishi, Ryozo, Fujiwara, Michihiro
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Sprache:eng
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Zusammenfassung: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-HT2A receptors. Endocannabinoid and glutamatergic systems have been suggested to modulate the function of 5-HT2A 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. ► Endocannabinoid system modulates DOI-induced head-twitch response (HTR).► AMPA receptor antagonist inhibits DOI-induced HTR.► AMPA receptor positive modulator reverses inhibition of HTR by NBQX and URB597.► Endocannabinoid and glutamatergic systems participate in the mechanism of DOI.
ISSN:0091-3057
1873-5177
DOI:10.1016/j.pbb.2011.04.003