Cyclooxygenase-2 inhibition reduces anxiety-like behavior and normalizes enhanced amygdala glutamatergic transmission following chronic oral corticosterone treatment

Amanda Morgan, Veronika Kondev, Gaurav Bedse, Rita Baldi, David Marcus, Sachin Patel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Chronic stress increases the probability of receiving an anxiety, depression, or chronic illness diagnosis. Pharmacological interventions that reduce the behavioral and physiological effects of chronic stress in animal models may represent novel approaches for the treatment of stress-related psychiatric disorders. Here, we examined the effects of cyclooxygenase-2 (COX-2) inhibition on anxiety-like behaviors and amygdala glutamatergic signaling after chronic non-invasive oral corticosterone (CORT) administration in mice. Treatment with the highly selective COX-2 inhibitor Lumiracoxib (LMX) reversed anxiety-like behavior induced by chronic CORT. Specifically, acute and repeated administration of LMX 5 mg kg−1 reduced chronic CORT-induced anxiety-like behavior measured using the elevated-plus maze, elevated-zero maze, and light-dark box tests. In contrast, LMX did not affect anxiety-like behaviors in naïve mice. Ex vivo electrophysiology studies revealed that repeated LMX treatment normalized chronic CORT-induced increases in spontaneous excitatory glutamatergic currents recorded from anterior, but not posterior, basolateral amygdala neurons. These data indicate COX-2 inhibition can reverse chronic CORT-induced increases in anxiety-like behaviors and amygdala glutamatergic signaling, and support further clinical investigation of selective COX-2 inhibitors for the treatment of affective and stress-related psychiatric disorders.

Original languageEnglish (US)
Article number100190
JournalNeurobiology of Stress
Volume11
DOIs
StatePublished - Nov 2019
Externally publishedYes

Keywords

  • Anxiety
  • Basolateral amygdala
  • Cyclooxygenase-2
  • Stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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