Functional relationships, previous history and the discrimination of a drug mixture in rats

AND and AND-OR drug mixture discriminations in rats: generalization to single drugs and drug mixtures

“…Firstly, generalization from the mixture to the single drugs nicotine, cocaine, ca¤eine, midazolam and ethanol has been examined in two groups of rats, trained under AND-and AND-OR discrimination procedures, respectively. Dose-response curves for the training drugs amphetamine and pentobarbitone given separately were not developed in the present experiments, since such data have been reported previously in several studies; in each case under the AND-discrimination procedure (Mariathasan et al 1991Mariathasan and Stolerman 1994), there was full, dose-related, generalisation to either training drug given alone but no such generalisation under AND-OR conditions (Stolerman and Mariathasan 1990;Mariathasan and Stolerman 1994). Secondly, tests of generalization to drug mixtures have been carried out with one of the drugs changed and with the other drug the same as in the training mixture (single substitution tests); here, the e¤ects of changing the stimulant component from amphetamine to either nicotine or cocaine has been examined with the depressant (i.e.…”

“…Training was based on the procedures of Mariathasan and Stolerman (1994). After 3 weeks of preliminary training to establish a baseline of responding under a Þxed ratio (FR-10) schedule, both levers were made available simultaneously and discrimination training began.…”

“…Typically, marked and sometimes complete generalization has been obtained from the mixtures used for training to their component drugs given singly Mariathasan et al 1991;. In other studies, the inßuence of one of the drugs in the training mixture on the dose-response curve for the second drug has been examined and evidence for some supra-additive interactions has been reported (Mariathasan and Stolerman 1994;Mariathasan et al 1996).…”

“…Initial studies with AND-OR procedures used mixtures of amphetamine plus pentobarbitone; generalization tests showed that there was no mixtureappropriate responding produced by any dose tested of the individual drugs, and it was suggested that AND-OR discrimination training may have enhanced pharmacological speciÞcity (Stolerman and Mariathasan 1990;Mariathasan and Stolerman 1994). Experiments on the discrimination of a nicotine plus midazolam mixture with the antagonists mecamylamine and ßumazenil supported this idea; the antagonists attenuated the mixture discrimination to a greater extent and at much smaller doses under AND-OR than under AND-discrimination training conditions (Mariathasan et al 1997).…”

“…The current experiments investigate further the features of stimulus generalization in rats trained to discriminate drug mixtures; speciÞcally, these studies examine how di¤erent functional relationships between responses, drugs and reinforcers established by training subjects in di¤erent ways may impact upon generalizations to novel drugs and drug mixtures. Earlier studies have established that the choice between AND-or AND-OR discrimination training procedures can markedly inßuence other characteristics of discriminations based upon drug mixtures (Stolerman and Mariathasan 1990;Mariathasan and Stolerman 1994;Mariathasan et al 1997).…”