Diazepamの乳仔期連続投与によるラット中枢神経系機能発達の変化

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Wistar-Imamichi male rats were treated daily with diazepam (s.c.) in a dose of 0.2, 2, 5 mg/kg (D0.2-, D2-or D5-rats) or 5%EtOH, beginning on the 8th day until the 20th day after birth. 1) The developmental pattern of the coordinated motor activity in D-rats did not show any significant alteration from that in controls. 2) D2- and D5-rats showed a significant decrease in the activity counts of ambulation and rearing at 16 and 19 days of age in the open-field test. With acute administration of 0.5 mg/kg diazepam (i.p.) at 20 days of age, however, the decrease in the counts of ambulation and rearing was significantly lower in D-rats than that in normal and 5%EtOH-rats. 3) At 5 weeks of age, the effect of acutely administered diazepam (2 mg/kg, i.p.) was also less marked in D-rats. Incidences of ataxia by diazepam were 71.4% in D0.2, 33.3% in D2-rats and 88-100% in controls at 10 min. Thirty min later, none of the D-rats showed ataxia. 4) At 7 weeks of age, there was no significant difference in the response to acute diazepam administration among the groups. No effect of diazepam on the body growth and the time of eye-opening was detected. The present results indicate that chronic treatment with rather small doses of diazepam during an infantile period in the rat induces a long-lasting tolerance to diazepam.
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