title: Functional role of the endocannabinoid system and AMPA/kainate receptors in 5-HT2A receptor-mediated wet dog shakes.
abstract: These experiments sought to determine the influence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors and the endocannabinoid system in the functional expression of the serotonin (5-HT) type 2A receptor-mediated wet dog shake response. Male Long-Evans rats were pretreated with either 1 mg/kg i.p. of the 5-HT(2A/2C) receptor antagonist ketanserin; 1, 10 or 30 mg/kg i.p. of the AMPA/kainate antagonist 6,7-dinitroquinnoxaline-2,3-dione (DNQX); 1, 5 or 10 mg/kg i.p. of the endocannabinoid uptake inhibitor AM404; or 1, 5 or 10 mg/kg i.p. of the cannabinoid CB(1) receptor antagonist AM 251 prior to injection of the 5-HT(2A/2C) receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI, 1 mg/kg i.p.). Results demonstrated that 10 mg/kg of AM404 significantly reduced the expression of DOI-induced wet dog shakes, but lower doses were ineffective. Administration of AM251 did not induce wet dog shakes behavior when administered alone, but significantly potentiated DOI-induced wet dog shaking behavior at a dose of 10 mg/kg. Pretreatment with DNQX significantly reduced the expression of DOI-induced wet dog shakes at all doses tested. These data suggest that AMPA/kainate receptors play a role in the mediation of 5-HT(2A) receptor activity, whereas the endocannabinoid system may act as a regulatory buffer system during periods of elevated activity, but not under basal conditions.
authors.affiliation: Department of Psychology, University of British Columbia, 2136 West Mall, Vancouver, B.C., Canada V6T 1Z4. bgorzalka@psych.ubc.ca
authors.forename: Boris B
authors.initials: BB
authors.lastname: Gorzalka
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Hill
authors.forename: Jane C
authors.initials: JC
authors.lastname: Sun
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D063385:Cannabinoid Receptor Modulators / Q000037:antagonists & inhibitors / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists; D007650:Ketanserin; D010880:Piperidines; D011720:Pyrazoles; D011810:Quinoxalines; D044402:Receptor, Serotonin, 5-HT2A; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D017366:Serotonin Receptor Agonists; C103505:AM 251; C056723:FG 9041; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C107594:N-(4-hydroxyphenyl)arachidonylamide