新生仔期ミダゾラム投与がラットの社会性行動に及ぼす影響、およびメチルフェニデート急性投与によるその回復

抄録

There has been growing evidence suggesting disturbances in the neonatal period, including exposure to anesthetics and sedatives, cause neurodevelopmental disorders long after the causative event. In this study, we investigated the effect of neonatal treatment with midazolam, an allosteric agonist of gamma-Aminobutyric acid (GABA)_A receptor that bind to benzodiazepine receptor, on spontaneous activity and sociability in social recognition test in adulthood. In the social recognition test, rats were allowed to explore an open field where unfamiliar individual (to-be familiar individual) were presented (sample phase, 5 min), and after a delay of 30 min they were placed again in the same arena where familiar individual and novel individual were placed (test phase, 5 min). Midazolam (50 mg/kg) treatment from 5 to 7 days after birth increased social interaction duration and decreased social discrimination ratio, i.e. decreased preference to the novel individual in the social recognition test. Furthermore, acute systemic administration of methylphenidate (1.5 mg/kg), dopamine and noradrenaline reuptake inhibitor, 30 min prior to sample phase recover the decrement of discrimination ratio in the rats neontally treated with midazolam. Results suggest that neural circuits whose development are disrupted by neonatal midazolam treatment are associated with sociability, and at least partially modified by dopamine and noradrenaline.