title: Role of social encounter-induced activation of prefrontal serotonergic systems in the abnormal behaviors of isolation-reared mice.
abstract: Isolation-reared male rodents show abnormal behaviors such as hyperlocomotion, aggressive behaviors, deficits of prepulse inhibition, and depression- and anxiety-like behaviors, but the neurochemical mechanism for the effects of psychological stress in these animals is not fully understood. This study examined the effects of social interactions between isolation-reared mice and intruder mice on brain monoaminergic systems. A cage was divided into two compartments by a mesh partition to prevent direct physical interactions. The 20-min encounter with an intruder elicited a restless and hyperexcitable state (hyperactivity) in male, but not in female, isolation-reared mice, whereas encounters with a sleeping intruder or a novel object did not. Although the encounter did not affect prefrontal neuronal-activity-marker c-Fos expression, dopamine (DA) levels, or serotonin (5-HT) levels in male group-reared mice or female isolation-reared mice, it increased prefrontal c-Fos expression, DA levels, and 5-HT levels in male isolation-reared mice. Furthermore, encounter-induced increases in c-Fos expression in the dorsal raphe nucleus and ventral tegmental area, but not in the nucleus accumbens shell, were much greater in isolation-reared than group-reared male mice. A 5-HT1A receptor agonist, a metabotropic glutamate 2/3 receptor agonist, and a gamma-aminobutyric acid A receptor agonist attenuated isolation-induced aggressive behaviors and encounter-induced hyperactivity, c-Fos expression in the prefrontal cortex and dorsal raphe nucleus, and increases in prefrontal 5-HT levels. These findings suggest that the prefrontal DA and 5-HT systems are activated by encounter stimulation in male isolation-reared mice, and the encounter-induced activation of 5-HT system triggers the induction of some abnormal behaviors in male isolation-reared mice. Furthermore, this study implies that the encounter stimulation-induced signal has a pharmacological significance.
authors: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
authors: Yukio
authors: Y
authors: Ago
authors: Ryota
authors: R
authors: Araki
authors: Tatsunori
authors: T
authors: Tanaka
authors: Asuka
authors: A
authors: Sasaga
authors: Saki
authors: S
authors: Nishiyama
authors: Kazuhiro
authors: K
authors: Takuma
authors: Toshio
authors: T
authors: Matsuda
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D005260:Female; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012934:Social Isolation / Q000523:psychology*
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004146:Dioxanes; D004149:Dioxoles; C118218:LY 379268; D012701:Serotonin; C096294:osemozotan