Effects of sodium phenobarbital on motor activity and exploration in the mouse: Development of tolerance and incidence of withdrawal responses

Abstract

Sodium phenobarbital (20 mg/kg) was without significant effect on exploratory head-dipping, but a higher dose (70 mg/kg) significantly reduced the number of head-dips and the time spent head-dipping 0.5 and 8 hr after acute administration. Tolerance developed rapidly, i.e., by day 7 of treatment, to these reductions. Both doses of phenobarbital significantly increased locomotor activity, the increase was more marked for the 70 mg/kg dose and for this dose was greater 8 hr after administration than 0.5 hr. No tolerance developed over 21 days of treatment to the increase in locomotor activity 0.5 hr after drug administration; some tolerance did develop by day 14 to the increase detected 8 hr after drug administration, but this is likely to be metabolic. After 21 days of treatment, sodium phenobarbital was withdrawn. Twenty-four hours after the last dose of 70 mg/kg there was a significant reduction in the time spent head-dipping; there was also significant reduction in locomotor activity, which peaked 48 hr after the last dose.