EFFECTS OF DIAZEPAM ON CONDITIONED TASTE AVERSIONS IN RATS

JOHN DAVID ROACHE, Purdue University

Abstract

Conditioned taste aversion (CTA) is the learned avoidance of the ingestion of a distinctively-tasting fluid which has previously been associated with a punishing, aversive drug experience. Anxiolytic agents, known to reduce avoidance in shock-motivated procedures, were tested for their ability to antagonize CTA's in rats. Taste aversions to a saccharin solution (0.1%, w/v) were conditioned with LiCl (3 mEq/kg) in male, Sprague-Dawley rats which were chronically adapted to a 23-hour fluid-deprivation schedule. The objective of these experiments was to determine whether diazepam (or more generally, the anxiolytic benzodiazepines) would specifically disinhibit the suppressed saccharin drinking of rats with a CTA to the fluid. Using a two-bottle, free-choice paradigm where rats had a simultaneous access to both distilled water and the saccharin solution, conditioned rats avoided saccharin and drank water almost exclusively whereas control animals preferred saccharin. Under these conditions, acute diazepam treatment (6, 9, 12 mg/kg) significantly attenuated CTA's to saccharin but the effect was moderate in degree and conditioned rats continued to prefer water over saccharin. Chlordiazepoxide (9, 12 mg/kg) also attenuated CTA's in this paradigm but was less potent that diazepam. Diazepam also attenuated CTA's to a more concentrated saccharin solution (0.25%, w/v) indicating that the effect was applicable to saccharin solutions in general. Both hypertonic saline (16%, w/v, NaCl) and sodium barbital (100 mg/kg) produced polydipsia without significantly affecting the CTA's indicating that the anxiolytic benzodiazepines attenuate CTA's by mechanisms apparently independent of their dipsogenic actions. Repeated diazepam injections (9, 12 mg/kg) over five days promoted extinction of the CTA's and resulted in actual saccharin preferences over water in conditioned rats. However, when diazepam treatment was terminated, these same animals again avoided saccharin intake and preferred water. Overall, the results of the present series of investigations support the hypothesis that diazepam (or more generally, the anxiolytic benzodiazepines) exerts its characteristic disinhibitory effects in the CTA paradigm and antagonizes the manifestation of a formerly established CTA in rats. With repeated diazepam treatments, extinction of the CTA's are promoted. However, the diazepam-induced CTA extinction is drug-state dependent and therefore conditioned rats do not truly learn to overcome their aversions.

Degree

Ph.D.

Subject Area

Psychobiology

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