title: p-Hydroxyamphetamine causes prepulse inhibition disruption in mice: contribution of serotonin neurotransmission.
abstract: p-Hydroxyamphetamine (p-OHA) has been shown to have a number of pharmacological actions, including causing abnormal behaviors such as increased locomotor activity and head-twitch response in rodents. We have recently reported that intracerebroventricular (i.c.v.) administration of p-OHA dose-dependently induces prepulse inhibition (PPI) disruption in mice, which is attenuated by pretreatment with haloperidol, clozapine or several dopaminergic agents. Haloperidol and clozapine have affinities for serotonergic (especially 5-HT(2A)) receptors. To investigate the involvement of the central serotonergic systems in p-OHA-induced PPI disruption, herein we tested several serotonergic agents to determine their effects on p-OHA-induced PPI disruption. p-OHA-induced PPI disruption was attenuated by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, a neurotoxin which targets serotonin-containing neurons) and p-chlorophenylalanine (PCPA, a serotonin synthesis inhibitor). p-OHA-induced PPI disruption was also attenuated by pretreatment with ketanserin (a 5-HT(2A/2C) receptor antagonist) and MDL100,907 (a selective 5-HT(2A) receptor antagonist). These data suggest that p-OHA-induced PPI disruption may involve increased serotonin release into the synaptic cleft, which then interacts with the post-synaptic 5-HT(2A) receptor.
authors.affiliation: Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onogi
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawasai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Satoru
authors.initials: S
authors.lastname: Mitazaki
authors.forename: Kota
authors.initials: K
authors.lastname: Nakaya
authors.forename: Kenya
authors.initials: K
authors.lastname: Watanabe
authors.forename: Fukie
authors.initials: F
authors.lastname: Niijima-Yaoita
authors.forename: Koichi
authors.initials: K
authors.lastname: Tan-No
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Arai
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tadano
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000009:adverse effects; D000161:Acoustic Stimulation / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D010134:Fenclonine / Q000494:pharmacology; D005464:Fluorobenzenes / Q000494:pharmacology; D007266:Inhibition, Psychological; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D013216:Reflex, Startle / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000009:adverse effects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013997:Time Factors; D010136:p-Hydroxyamphetamine / Q000494:pharmacology*
chemical_list: D005464:Fluorobenzenes; D010880:Piperidines; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D007650:Ketanserin; C079049:volinanserin; D010136:p-Hydroxyamphetamine; D010134:Fenclonine