Antagonism of AND and AND-OR drug mixture discriminations in rats |
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Affiliation: | 1. Department of Experimental Psychology and Helmholtz Institute, Utrecht University, Utrecht, the Netherlands;2. Altrecht Academic Anxiety Center, Utrecht, the Netherlands;3. Brain Research & Innovation Center, Ministry of Defence, Utrecht, the Netherlands;4. Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands;5. Vrije Universiteit Amsterdam, VUmc medical faculty, Amsterdam, the Netherlands;6. Department of Methodology and Statistics, Tilburg University, Tilburg, the Netherlands;7. University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands;8. GGZ Drenthe, Department of specialist trainings, Assen, the Netherlands;9. Department of Pharmaceutical Sciences, Division of Pharmacology, UIPS, Utrecht University, Utrecht, the Netherlands |
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Abstract: | It has been suggested that use of the AND-OR training method may be associated with an enhancement of the pharmacological specificity of discriminations based on mixture of drugs. Rats were trained to discriminate a mixture of nicotine (0.4 mg/kg s.c.) plus midazolam (0.2 mg/kg s.c.) from saline (AND-discrimination, n = 8) or to discriminate the mixture from either drug alone (AND-OR discrimination, n = 6). The studies used two-lever operant procedures with food reinforcers presented on a tandem schedule. After discriminations were acquired to 80% accuracy, the nicotine antagonist mecamylamine (0.03–1.0 mg/kg s.c.) and the benzodiazepine antagonist flumazenil (0.32–10 mg/kg i.p.) were tested on the response to the mixture of nicotine plus midazolam. The antagonist effects of either mecamylamine or flumazenil given alone were more marked in rats trained under the AND-OR procedure than in rats trained on the AND-discrimination. Similarly, the antagonist effects of mixtures of mecamylamine plus flumazenil were much more potent under the AND-OR than under the AND-discrimination procedure. The AND-OR method reduced the dose of the antagonist mixture needed to produce complete block by a factor of about 10, as compared with the AND-discrimination. These striking differences in sensitivity to antagonists support the view that AND-OR or related procedures may enhance the pharmacological specificity of complex drug discriminations. |
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