Ketamine facilitates extinction of avoidance behavior and enhances synaptic plasticity in a rat model of anxiety vulnerability: Implications for the pathophysiology and treatment of anxiety disorders

Neuropharmacology
Ashley M FortressKevin C H Pang

Abstract

Anxiety disorders and posttraumatic stress disorder (PTSD) share a common feature of pathological avoidance behavior. The Wistar Kyoto (WKY) rat has been used as a model of anxiety vulnerability, expressing a behaviorally inhibited temperament, acquiring avoidance behavior more rapidly and displaying extinction-resistant avoidance compared to Sprague Dawley (SD) rats. Subanesthetic levels of ketamine have gained attention as a rapid antidepressant in treatment-resistant depression. While traditional antidepressants are commonly used to treat anxiety disorders and PTSD, the therapeutic utility of ketamine for these disorders is much less understood. The hippocampus is critical for the actions of antidepressants, is a structure implicated in anxiety disorders and PTSD, and is necessary for extinction of avoidance in SD rats. WKY rats have impaired hippocampal long-term potentiation (LTP), suggesting that persistent avoidance in WKY rats may be due to deficient hippocampal synaptic plasticity. In the present study, we hypothesized that ketamine would facilitate extinction of avoidance learning in WKY rats, and do so by enhancing hippocampal synaptic plasticity. As predicted, ketamine facilitated extinction of avoidance behavior in...Continue Reading

Citations

Jul 25, 2019·Neuroscience and Biobehavioral Reviews·Lily R AleksandrovaAnthony G Phillips
Aug 31, 2019·Pharmacology & Therapeutics·Simone B Sartori, Nicolas Singewald
Jan 27, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Gabriela P SiloteVanessa Beijamini
Feb 20, 2021·Neuropeptides·Priti Ramakant Gupta, Kedar Prabhavalkar
Apr 1, 2021·Life Sciences·Máira Tereza Talma ChíricoRodrigo Cunha Alvim de Menezes
Aug 2, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Agnes NorburyAdriana Feder

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