Perceptual masking of the chlordiazepoxide discriminative cue by both caffeine and buspirone

Abstract

Twelve male Sprague-Dawley rats were traitrained to discriminate between the interoceptive stimulus attributes of 5 mg/kg chlordiazepoxide (CDP) and saline in a two-lever operant task under a fixed-ratio 10 (FR-10) schedule of food reinforcement. Caffeine, buspirone, and Ro 15-1788 failed to engender complete generalization when tested in combination with saline. In drug interaction test sessions caffeine (56 mg/kg) blocked the discriminative stimulus properties of the training dose of CDP and shifted the CDP discriminative dose-response function to the right. This rightward shift in CDP discriminative function was paralleled by a concomitant downward shift in the rate-of-responding dose-response function. Drug interaction test sessions conducted with 3.2 mg/kg of buspirone in combination with various doses of CDP engendered a downward shift in both the discriminative and rate-of-responding dose-response functions. Because 3.2 mg/kg buspirone in combination with the training dose of CDP resulted in complete response rate suppression, additional combination tests were conducted with 3 mg/kg CDP, a dose which reliably engendered >90% CDP-appropriate responding, and various doses of buspirone. Similar to the CDP-caffeine interactions, buspirone blocked the cueing properties of 3 mg/kg CDP with a parallel reduction in response rates. Interaction test sessions conducted with Ro 15-1788 and CDP resulted in rightward shifts in both the discriminative and rate functions of CDP. We suggest that the interactions between CDP and both caffeine and buspirone resulted from the perceptual masking of the interoceptive (subjective) effects of CDP, whereas the interaction between Ro 15-1788 and CDP reflect pharmacological antagonism.