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.
Smith
R L
RL
John F. Kennedy Center, Vanderbilt University, Nashville, TN 37203, USA.
Barrett
R J
RJ
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005502:Food; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012107:Research Design
D014151:Anti-Anxiety Agents; D003975:Diazepam