Interoceptive stimuli produced by an anxiogenic drug are mimicked by benzodiazepine antagonists in rats pretreated with isoniazid.

Treatments which increase gamma-aminobutyric acid (GABA) neurotransmission or those which cause stimulation of benzodiazepine receptors, produce anxiolytic effects; but the converse (anxiogenic) effects have not been reported after suppression of either system alone. We report here that simultaneous inhibition of these two systems produces anxiogenic effects. After partial depletion of GABA by isoniazid, the benzodiazepine antagonists, RO 15-1788 and CGS8216, produced pentobarbital reversible anxiogenic effects in the pentylenetetrazol discrimination assay. These results support the hypothesis that GABA and endogenous anxiolytics mutually facilitate modulation of anxiety. They also indicate that there may exist endogenous anxiogenics which act at non-benzodiazepine recognition sites.