Multiple drug training as a method for increasing the specificity of the drug discrimination procedure.

In a two-lever appetitively reinforced bar-pressing task, one group of rats learned a phenobarbital vs. saline discrimination. Groups 2 to 4 were reinforced for pressing one lever when given phenobarbital and for pressing the other level when given saline or any one of three drugs. In Group 2, the other drugs were the stimulants amphetamine, cocaine and bemegride. In Group 3, the other drugs lacked either strong stimulant or depressant effects (fentanyl, nicotine and cyclazocine). In Group 4, the other drugs were the depressants ethanol, chlordiazepoxide and ketamine. All rats learned the required multiple drug (phenobarbital vs. other) discrimination after one to four training sessions per drug. After discrimination training was completed, tests for substitution with various depressant drugs showed that the degree to which these drugs substituted for phenobarbital differed greatly across groups. Substitution was most complete in rats trained with phenobarbital vs. saline and least complete when the other training drugs were depressants. The results indicate that the degree of specificity produced by phenobarbital vs. other drug discrimination training can be systematically altered by varying the drugs included in the other category.