Discriminative stimulus control by the anxiogenic beta-carboline FG 7142: generalization to a physiological stressor

Drug discrimination was employed to investigate the similarities between FG 7142-induced anxiogenesis and the stress produced by exposure to either a novel environment or to footshock. Eight rats were trained to discriminate between the stimulus properties of the beta-carboline FG 7142 (5.0 mg/kg) and its vehicle in a two-lever, food motivated operant task. Once trained, decreasing doses of FG 7142 produced fewer FG 7142-appropriate responses and the dose-response relationship yielded an ED50 of 1.45 mg/kg. Rats were subsequently subjected to two physiological/environmental stressors, footshock and novelty, and then tested in the discriminative paradigm. Exposure to novelty resulted in partial FG 7142-appropriate responding, whereas footshock sessions produced responding predominately on the FG 7142-appropriate lever. This is the first report of stimulus control by FG 7142 and it is likely that the interoceptive cue state produced by this compound is anxiogenic in nature, as reported to occur in man. The anxiogenic nature of the FG 7142 discriminative stimulus is supported by the generalization of FG 7142 to the state produced following stressful environmental manipulation.