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Relative reinforcing effects of different benzodiazepine doses for rhesus monkeys
Thomas H Gomez1, John D Roache, Richard A Meisch
1Substance Abuse Research Center, Department of Psychiatry and Behavioral Sciences, Medical School, University of Texas-Houston Health Science Center, 1300 Moursund Street, Houston, TX 77030-3497, USA.
Abstract:
The relative reinforcing effects of different doses of benzodiazepines were determined by giving rhesus monkeys concurrent access to different diazepam and midazolam concentrations. For each monkey a dose response function was obtained using three drug concentrations: low (L), intermediate (I), and high (H). The benzodiazepine and the water vehicle were concurrently available under independent fixed-ratio (FR) schedules. After establishing that each concentration was a reinforcer in comparison to vehicle, relative preference for the different concentrations was examined by making pairs of concentrations concurrently available under independent FR schedules. Three pairs were studied (H vs. L, H vs. I, and I vs. L). With both drugs, higher concentrations maintained greater response rates than lower concentrations. Thus, relative reinforcing effects increased with dose. These findings are similar to those obtained with other reinforcing drugs and provide further evidence that benzodiazepines share significant characteristics with other drug reinforcers. Importantly, absolute response rates (responses per session) obtained when only one drug dose was present were not reliably predictive of subsequent preferences for the dose. Both benzodiazepines served as effective reinforcers in that consistent levels of responding were maintained across doses and above vehicle levels under concurrent FR 32 schedules. As with other reinforcing drugs, the reinforcing effects of benzodiazepines increase with increases in dose over a broad range of values.