Chronic administration of S-(-)-pentobarbital in pigeons and rats: tolerance development

The development of tolerance to pentobarbital and cross-tolerance to other barbiturates has been documented in both laboratory animals and man. This study was undertaken to determine the extent of tolerance development to S-(-)-pentobarbital in rats and pigeons receiving 10 mg/kg/day S-(-)-pentobarbital, PO. In addition, the extent of cross-tolerance was determined to R-(+)-pentobarbital and both isomers of secobarbital. Rats were trained to respond under a variable-interval 60-sec (V160) schedule of food presentation while pigeons were trained to respond under a multiple fixed-ratio 30, fixed-interval 600-sec schedule of food presentation. After responding had stabilized, dose-response curves were determined for R-(+)-pentobarbital, S-(-)-pentobarbital, R-(+)-secobarbital, and S-(-)-secobarbital in both species. Upon the completion of the acute dose-response curves, both rats and pigeons were given 10 mg/kg/day S-(-)-pentobarbital, PO for 30 consecutive days prior to the redetermination of all four dose-response curves. Upon the completion of this second determination of each curve, the daily administration of the S-(-)-pentobarbital was discontinued, and the rats and pigeons remained drug free for 30 days. Following this 30-day drug free period, dose-response curves for the isomers of both pentobarbital and secobarbital were redetermined for a third time.(ABSTRACT TRUNCATED AT 250 WORDS)