The purpose of this study was to determine the effects of the schedule of reinforcement on a pentobarbital discrimination in rats. Five rats were trained to discriminate 10 mg/kg pentobarbital from saline under a multiple fixed-interval 180-s fixed-ratio 20 schedule of reinforcement. During both saline and pentobarbital training sessions, subjects emitted a higher percentage of correct responses under the fixed-ratio component as compared to the fixed-interval component of the multiple schedule. Determination of the pentobarbital dose-response curve under the fixed-ratio component resulted in a steep curve characterized by responding on the saline lever at low doses and on the drug lever at higher doses. Under the fixed-interval component, a graded dose-effect curve was produced, with considerable responding on both levers after intermediate doses of pentobarbital. The administration of phencyclidine and MK-801 resulted in an intermediate level of drug-lever responding for some subjects. Administration of d-amphetamine resulted in saline (nondrug) appropriate responding. The results of this study demonstrate that the schedule of reinforcement is a determinant of drug stimulus control, just as it is a determinant of other drug effects.

Three pigeons were trained to discriminate a 5.0 mg/kg dose of pentobarbital from saline under a two-key concurrent schedule with responding on the key associated with the presession injection, under both stimulus conditions, producing four times as many reinforcers as responding on the other key. This concurrent schedule resulted in approximately 70% responding to the higher reinforcement key under the pentobarbital stimulus and approximately 30% responding to that key under the saline stimulus. During testing, then, the pigeons were able to dose-dependently emit higher (>70%) or lower (<30%) values than were established under the control conditions. Doseresponse curves were determined for pentobarbital (twice), methamphetamine, phencyclidine, chlordiazepoxide, and the combination of pentobarbital and the barbiturate antagonist bemegride. The results obtained with pentobarbital and chlordiazepoxide showed that, as the dose increased, pentobarbital-appropriate responding also increased. Methamphetamine produced relatively flat dose-response curves, whereas phencyclidine administration produced inconsistent effects on responding. The combination of the training dose of pentobarbital with increasing doses of bemegride produced a decrease in pentobarbital-appropriate responding. The results also showed that the doseresponse curves for pentobarbital and chlordiazepoxide, instead of being all or none, were graded functions of the drug dose.

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