title: Involvement of prefrontal AMPA receptors in encounter stimulation-induced hyperactivity in isolation-reared mice.
abstract: We recently showed that social encounter stimulation induces hyperactivity in mice reared in social isolation from early life and this is associated with the transient activation of prefrontal dopaminergic and serotonergic systems. In the present study, we examined the effect of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 2, 3-dioxo-6-nitro-1, 2, 3, 4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) on encounter-induced behavioural and neurochemical changes to study the role of the receptor in abnormal behaviours in isolation-reared mice. The encounter to an intruder mouse induced hyperactivity with transient increases in prefrontal dopamine and serotonin levels in isolation-reared mice. NBQX attenuated the encounter-induced hyperactivity and the associated neurochemical changes in isolation-reared mice. In addition, NBQX reduced aggressive behaviour and cognitive impairment in isolation-reared mice, but did not affect depressive-like behaviour or spontaneous hyper-locomotion in these animals. The AMPA receptor agonist (S)-AMPA increased prefrontal dopamine and serotonin release, and this effect was higher in isolation-reared mice than in the group-reared mice, suggesting higher prefrontal AMPA receptor activity in isolation-reared mice. Furthermore, isolation rearing increased the expression of AMPA receptor subunits (GluR1, GluR2 and GluR3) and GluR1 Ser845 phosphorylation in the prefrontal cortex, but not in the hippocampus or nucleus accumbens. Taken together, these results suggest that an increase in AMPA receptor activity in the prefrontal cortex contributes to some, but not all, abnormal behaviours in isolation-reared mice.
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Araki
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hasebe
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Nishiyama
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000502:physiology / Q000523:psychology; D000818:Animals; D021461:Animals, Outbred Strains; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D003863:Depression / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006948:Hyperkinesis / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D051379:Mice; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012919:Social Behavior; D012934:Social Isolation / Q000523:psychology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D012701:Serotonin; D004298:Dopamine