Assessment of the stimulus properties of anxiolytic drugs by means of the conditioned taste aversion procedure.
The conditioned taste aversion (CTA) procedure has recently been described as a more rapid alternative to two-lever operant procedures in drug discrimination research. We trained different groups of rats to discriminate the benzodiazepine chlordiazepoxide (CDP, 20 mg/kg) or the 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.4 mg/kg) from saline by means of the CTA procedure. The results were in agreement with findings from two-lever operant drug discrimination procedures. However, discrimination training took 40 sessions in the case of CDP and 72 sessions for 8-OH-DPAT, which is comparable to results obtained with two-lever operant procedures. Dose-response curves were determined and generalization tests were performed for different benzodiazepine and nonbenzodiazepine anxiolytics. Baseline behavior deteriorated in the course of generalization and substitution testing, thus preventing further generalization testing. Our experience is that the use of the CTA procedure in drug discrimination research does not have sufficient advantages over traditionally used procedures to replace the latter.
Solvay-Duphar b.v., Department of Pharmacology, Weesp, The Netherlands.
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Van Hest
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Hijzen
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JL
Slangen
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Olivier
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005793:Generalization, Psychological / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D013649:Taste / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D012701:Serotonin; D002707:Chlordiazepoxide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008094:Lithium