Pentobarbital discrimination in the mouse.

Abstract

Mice have rarely been used for drug discrimination research. A procedure is described for training mice to discriminate sodium pentobarbital (PB) from vehicle and the pharmacological specificity of the PB stimulus was assessed by generalization testing with methohexital, ethanol, chlorpromazine and morphine. Mice were trained to discriminate PB from vehicle using a two-lever procedure with responding maintained under a fixed-ratio 20 schedule of milk presentation. Training was initiated with 10 mg/kg PB or saline given i.p. 20 min prior to the sessions, and stimulus control was assessed every third session during 2-min periods when responding on either lever was reinforced. After 48 training sessions, good stimulus control had not been achieved. The PB dose was increased to 15 mg/kg, and after 12 additional training sessions, a mean accuracy of 93.5% and 88.1% was obtained on PB and saline tests, respectively. Generalization tests for the time course of the PB stimulus indicated that over 90% PB-lever responding occurred with pretreatment times of 5, 10 and 20 min, falling to 25.6% by 40 min and 15.4% by 60 min. Dose-dependent generalization was also obtained with doses of 15, 20 and 30 mg/kg occasioning over 75% and doses of 5 and 10 mg/kg occasioning less than 25% PB-lever responding. The mice also generalized from PB to methohexital and ethanol, although with the latter greater than 90% PB-lever responding was only produced by a dose that substantially decreased overall rates of responding. Generalization was not obtained with morphine nor chlorpromazine. Typical drug discrimination procedures utilized for pigeons, rats and monkeys can also be used with mice.