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The antidepressant drug phenelzine produces antianxiety effects in the plus-maze and increases in rat brain GABA

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Abstract

Research on the effects of antidepressant/antipanic drugs in animal models of anxiety has yielded equivocal results, even after chronic drug regimens. In contrast, we found that the antidepressant/antipanic drug phenelzine, given acutely, produced a clear anxiolytic effect in the elevated plus-maze, a widely-used animal model of “anxiety” that is primarily sensitive to benzodiazepine-type anxiolytics (e.g., diazepam). Furthernore, the effective dose of phenelzine (15 mg/kg) administered to rats was associated with more than a 2-fold increase in whole brain levels of γ-aminobutyric acid (GABA), whereas an ineffective dose of phenelzine (5.1 mg/kg) did not significantly change GABA levels. TheN-acetylated metabolite of phenelzine,N 2-acetylphenelzine, produced neither an anxiolytic effect in the elevated plus-maze nor a significant change in whole-brain levels of GABA. However, both phenelzine andN 2-acetylphenelzine potently inhibited monoamine oxidase inhibitors such as phenelzine in the treatment of depression in humans. These results suggest that the mechanism whereby phenelzine produces anxiolytic effects in the plus-maze model is unique to a facilitatory action on brain levels of GABA, in contrast to classical benzodiazepines, which produce anxiolytic effects by enhancing the affinity of the GABAA-receptor for GABA.

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Authors and Affiliations

  1. Neurochemical Research Unit, Department of Psychiatry, University of Alberta, T6G 2B7, Edmonton, Alberta, Canada

    Teresa Paslawski, Glen B. Baker, Monica George & Ronald T. Coutts

  2. Department of Psychology, University of Alberta, T6G 2E9, Edmonton, Alberta, Canada

    Dallas Treit

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  1. Teresa Paslawski
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  2. Dallas Treit
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  3. Glen B. Baker
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  4. Monica George
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  5. Ronald T. Coutts
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Paslawski, T., Treit, D., Baker, G.B. et al. The antidepressant drug phenelzine produces antianxiety effects in the plus-maze and increases in rat brain GABA. Psychopharmacology 127, 19–24 (1996). https://doi.org/10.1007/BF02805970

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  • DOI: https://doi.org/10.1007/BF02805970

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