Chronic Vortioxetine Treatment Reduces Exaggerated Expression of Conditioned Fear Memory and Restores Active Coping Behavior in Chronically Stressed Rats

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DOI

  • Lauren Hatherall, Univ Texas Hlth Sci Ctr San Antonio, University of Texas Health San Antonio, University of Texas System, Ctr Biomed Neurosci
  • ,
  • Connie Sanchez
  • David A. Morilak, Univ Texas Hlth Sci Ctr San Antonio, University of Texas Health San Antonio, University of Texas System, Ctr Biomed Neurosci

Background: Stress is a risk factor for depression and anxiety disorders, disrupting neuronal processes leading to exaggerated fear and compromised coping behaviors. Current antidepressants are only partially effective. Vortioxetine, a novel multimodal antidepressant, is a serotonin transporter inhibitor; 5-HT3, 5-HT7, and 5-HT1D receptor antagonist; 5-HT1B partial agonist; and 5-HT1A agonist. We have shown that chronic dietary vortioxetine administration reversed stress-induced deficits in cognitive flexibility. In the present studies, we investigated the generality of vortioxetine's effects on other stress-related behavioral changes after different types of chronic stress.

Methods: In experiment 1, rats were fear-conditioned by pairing a tone with footshock, then exposed to chronic plus acute prolonged stress. In experiment 2, rats were exposed to chronic unpredictable stress. In both experiments, beginning on day 4 of chronic stress, vortioxetine was given in the diet (24 mg/kg/d). In experiment 1, effects of vortioxetine were tested on stress-induced changes in retention and extinction of cue-conditioned fear, and in experiment 2, on coping behavior on the shock probe defensive burying test after chronic stress.

Results: Chronic stress exaggerated the expression of conditioned fear memory. Vortioxetine restored fear memory to control levels and rendered extinction in stressed rats comparable with that in controls. In experiment 2, chronic unpredictable stress caused a shift from active to passive coping behavior, and vortioxetine restored active coping.

Conclusions: Vortioxetine reduced exaggerated expression of conditioned fear and restored adaptive coping behavior following 2 different types of chronic stress, adding to the evidence of its therapeutic potential in the management of depression and anxiety disorders.

Original languageEnglish
JournalInternational Journal of Neuropsychopharmacology
Volume20
Issue4
Number of pages8
ISSN1461-1457
DOIs
Publication statusPublished - 1 Apr 2017

    Research areas

  • coping, depression, fear memory, stress, vortioxetine, MAJOR DEPRESSIVE DISORDER, ANTIDEPRESSANT DRUG-TREATMENT, MEDIAL PREFRONTAL CORTEX, INTERMITTENT COLD STRESS, LU AA21004, MULTIMODAL ANTIDEPRESSANT, COGNITIVE DEFICIT, EXTREME STRESS, LATERAL SEPTUM, DOUBLE-BLIND

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