Drug Development Research zyx 14:85-90 (1988) Baclofen Does Not Block lnteroceptive Discriminative Stimulus Produced by Pentylenetetrazol Smart 0. ldemudia and Harbans La1 zyxwv Department of Pharmacology, Texas College of Osteopathic Medicine, Fort Worth ABSTRACT ldemudia S.O., and zyxwvu H. Lal.: zyxwvut Baclofendoes not block interoceptive discriminativestimulus produced by pentylenetetrazol.Drug Dev. Res. 14:85-90, 1988. Baclofen was compared with diazepam for ability to block the interoceptive discrimi- native stimulus produced by the anxiogenic drug pentylenetetrazol(PTZ). Male hooded rats of the Long Evans strain were trained in two-lever operant chambers to respond for food reward. Presses on one lever were reinforced after intraperitoneal injections of PTZ (20 mg/kg), and on the other lever after saline. After rats had acquired the PTZ discrimination, it was shown that pretreatment with baclofen failed to block the interoceptive stimulus produced by PTZ, whereas pretreatment with diazepam was effective. As baclofen is ineffective in a conflict procedure as well as in antagonizingthe PTZ stimulus, but produces a diazepamlike interoceptive discriminative stimulus, it is concluded that elicitation of the diazepam stimulus may not be related to diazepam’s anxiolytic efficacy and that diazepam discrimination may be an inappropriate model for studying anxiolytic properties of drugs. Furthermore,the difference between baclofen and diazepam with respect to anxiolytic efficacy is suggested to be related to receptor specificity. The binding of diazepam facilitates GABAA receptor activity, whereas the binding of baclofen facilitates GABAs receptors. Hence, it is suggested that modulation of GABAA receptors may be critical in diazepam’s blockade of the PTZ stimulus. Key words: drug discrimination, anxiolytic, anxiogenic, GABA receptors, diazepam, rat INTRODUCTION zyxwvuts In animal research on anxiety, conflict procedures have been used most extensively. In these procedures, anxiolytic efficacy of drugs is determined by their ability to reverse Received final version January 25, 1988; accepted April 11, 1988. Address reprint requests to Harbans Lal, Department of Pharmacology, Texas College of Osteopathic Medicine, 3516 Camp Bowie Blvd., Fort Worth, TX 76107-2690. Q 1988 Alan R. Liss, Inc.