Persistent electroencephalographic changes in rhesus monkeys after single doses of pentobarbital, nitrazepam and imipramine

Abstract

The immediate and persistent effects of single oral doses of sodium pentobarbital 20 mg/kg, nitrazepam 25 mg/kg and imipramine 25 mg/kg, were compared on behavioural patterns as well as on quantitative aspects of diurnal EEG patterns in rhesus monkeys. Consecutive pre-drug EEG recordings on agar treated monkeys, showed no significant variations in day to day EEG levels of wakefulness, drowsiness, sleep and the REM state. Both the sedative-hypnotic agents, sodium pentobarbital and nitrazepam, significantly reduced wakefulness and the REM state and increased slow wave sleep. They reduced the latency to onset of slow wave sleep but significantly increased the latency to onset of the REM state. The antidepressant agent imipramine, did not influence any of the EEG parameters to a significant extent. Significantly enhanced REM levels persisted during the 7-day post-drug period after cessation of medication of all three psychoactive agents. The effect on the macaque EEG of an increase in slow wave sleep with concomitant decreased levels of wakefulness and REM with respect to baseline levels, provides a quantitative basis for comparing sedative-hypnotic agents in monkeys. Residual drug-induced EEG changes, reflected by enhanced REM levels, may prove a sensitive indicator of persistent drug effects in subhuman primates.