Osmotic minipumps for administration of barbital to mice: demonstration of functional tolerance and physical dependence.

Sodium barbital was administered to mice at a constant rate by miniature osmotic pumps implanted subcutaneously. Each pump delivered approximately 0.25 mg/hr. With two pumps per mouse, blood barbital levels of 20 to 30 microgram/ml could be maintained for various periods. Barbital was assayed by gas chromatography. Functional tolerance was shown by a significant decrease in sleep time after a challenge dose of barbital administered 24 hours after withdrawal. Physical dependence was demonstrated by withdrawal hyperexcitability as measured either with pentylenetetrazol or by convulsions elicited by handling.