Influence of training paradigm on specificity of drug mixture discriminations.
Generalization to different drugs and drug mixtures has been examined in rats trained to discriminate a mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND discrimination, n = 8) or to discriminate the same mixture from its component drugs alone (AND-OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed-ratio 10 schedule of food reinforcement. There was partial generalization to nicotine and midazolam and no generalization to cocaine, caffeine, or ethanol under AND-discrimination conditions and no generalization to any of these drugs in the AND-OR discrimination. Nicotine or midazolam coadministered with the training doses of pentobarbitone and amphetamine, respectively, produced full generalization in the AND discrimination and partial generalization under AND-OR conditions. Cocaine coadministered with pentobarbitone generalized fully under both procedures, but at larger doses in the AND-OR than in the AND discrimination. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. The results consistently supported the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on drug mixtures.
Mariathasan
E A
EA
Section of Behavioural Pharmacology, Department of Psychiatry, Institute of Psychiatry, De Crespigny Park, London, UK.
Stolerman
I P
IP
White
J A
JA
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004193:Discrimination Learning; D004192:Discrimination, Psychological / Q000187:drug effects*; D004338:Drug Combinations; D005108:Extinction, Psychological / Q000187:drug effects; D005795:Generalization, Stimulus / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats
D000697:Central Nervous System Stimulants; D004338:Drug Combinations; D006993:Hypnotics and Sedatives; D010424:Pentobarbital; D003913:Dextroamphetamine