Midazolam's dose effects on fixed-ratio response rate in rats depend on amount of prior training experience.

To investigate the effects of amount of prior training on the operant response rate-decreasing effects of midazolam, the authors examined 6 oral (PO) doses of this drug (0.3, 1.0, 3.0, 10.0, 17.3, 30.0 mg/kg, 30 min before sessions) in 3 separate groups of rats (Rattus narvegicus). The rats received 29, 85, or 106 daily sessions (low, medium, and high groups, respectively) of fixed-ratio 30 water-reinforced training before the dose-effect determinations. Despite all 3 groups having had similar baseline response rates, the medium- and high-experience groups were significantly more sensitive to the rate-decreasing effects of the 3 highest doses of midazolam. All 3 groups were equally unresponsive (neither increasing nor decreasing response rate) to PO midazolam treatment at the 3 lowest doses. The experience-related sensitization to midazolam's behavior-disrupting effects suggests a role for amount as well as type of behavioral history as a determinant of behavioral drug effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)