AND and AND-OR drug mixture discriminations in rats: generalization to single drugs and drug mixtures.
BACKGROUND
Studies of the discriminative stimulus effects of drug mixtures provide an approach to polydrug abuse and studies on single drugs with multiple effects.


OBJECTIVE
This study was designed to investigate whether the use of the AND-OR procedure increases the specificity of drug mixture discriminations.


METHODS
Rats were 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.


RESULTS
Under AND-discrimination conditions, there was partial generalization to nicotine and midazolam when each drug was administered singly, and there was no generalization to cocaine, caffeine or ethanol. With the AND-OR discrimination, there was no generalization to any of the preceding drugs administered singly. In "single substitution" tests, nicotine or midazolam was co-administered with the training doses of pentobarbitone and amphetamine, respectively; there was full generalization in the AND-discrimination and partial generalization under AND-OR conditions. Cocaine co-administered with pentobarbitone generalized fully under both procedures, but the dose of cocaine needed was much larger in the AND-OR than in the AND-discrimination. In "dual substitution" tests, mixtures of two novel substances were tested. 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. Throughout the studies, in every instance where comparisons were made, generalization was greater or occurred at lower doses under AND- than under the AND-OR discrimination.


CONCLUSIONS
The study yielded extensive evidence supporting 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, Institute of Psychiatry, London, UK.
Stolerman
I P
IP
White
J A
JA
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D000431:Ethanol / Q000494:pharmacology; D005794:Generalization, Response / Q000187:drug effects*; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats
D014151:Anti-Anxiety Agents; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D004338:Drug Combinations; D018722:Nicotinic Agonists; D002110:Caffeine; D000431:Ethanol; D009538:Nicotine; D003042:Cocaine; D008874:Midazolam; D003913:Dextroamphetamine