On the mechanism of potentiation by morphine of thiopental sleeping time.

Injection of thiopental sodium, 25 or 40 mg/kg, i.p., into normal rats produced a prompt sleep which lasted 8.3 plus or minus 2.9 and 16.8 plus or minus 2.7 min, respectively. Injection of morphine sulphage, 20 mg/kg, i.p., itself produced only mild sedation but prolonged the thiopental induced sleep to 50 and 67.3 min, respectively. At 1 min after onset of sleep the brain thiopental concentration in morphine pretreated animals was significantly lower than in control animals. Furthermore the latter also awoke with higher brain thiopental concentrations; the morphine pretreated animals slept for a longer time despite lower brain thiopental concentration. The t1/2 of brain thiopental was longer in the morphine pretreated animals, 25 min, than in the control animals, 9 min. Distribution of thiopental in several tissues at various time periods following injection of thiopental revealed some time-related quantitative differences between the two groups but a similar qualitative pattern. It is suggested that morphine lowers the brain threshold for thiopental induced sleep.