Tolerance to the anticonflict effects of diazepam: importance of methodological considerations.

The present study examines the effects of chronic diazepam treatment on conflict behavior in rats using the Geller-Seifter paradigm. A dose-response function for the effects of diazepam (DZ) on punished and unpunished responding was determined (0.0, 0.63, 1.25, 2.5, and 5.0 mg/kg DZ intraperitoneally) using five independent groups. The test doses of DZ produced an inverted U-shaped function where punished responding increased as a function of dose up to 2.5 mg/kg and then decreased at 5.0 mg/kg. All groups were then treated with 2 x 5 mg/kg DZ per day for 5 days. When the dose-response function was redetermined at 36 h post-chronic treatment, it was found that the function had shifted to the right, indicating tolerance. Because of the inverted U-shaped nature of the original function, tolerance was manifested as a decrease in responding on the ascending portion of the function and as an increase in responding on the dose (5 mg/kg) representing the descending side of the inverted U.