Assessment of tolerance to barbital by means of drug discrimination procedures.

This study was designed to determine the relative development of tolerance to the discriminative-stimulus and hypnotic properties of barbital. By selectively reinforcing lever presses only in the presence of one of the drug stated, rats were trained in a Skinner Box to discriminate the effect of sodium barbital (80 mg/kg) injection from that of saline injection. After the rats were well trained, the administration of daily hypnotic doses of barbital (240 mg/kg) for 8 days produced marked tolerance to the hypnotic effect of the barviturate in all animals. The ability of the 80 mg/kg dose to serve as a discriminative stimulus was not impaired in animals which had been trained with the drug as the condition during which bar presses had been reinforced (SD condition). Animals for which bar presses had gone unrewarded under barbital (Sdelta condition) displayed a tendency to develop tolerance to the stimulus properties of barbital. These findings are interpreted in the light of dose-effect studies, and it is suggested that the acquired polarity of the drug condition determined by its assignment as Sd or Sdelta may influence the discriminability of the drug in future exposures.