Ketamine corrects a deficit in reversal learning caused by chronic intermittent cold stress in female rats

Denisse Paredes, Jeri D. Silva, David A. Morilak

Research output: Contribution to journalArticle

Abstract

Background: Individuals with stress-related psychiatric disorders exhibit deficits in cognitive flexibility. We have shown that chronic intermittent cold stress induces deficits in reversal learning, a form of cognitive flexibility mediated in the orbitofrontal cortex, that was reversed by ketamine in male rats. Such effects have not been tested in females. In this study, we examined effects of chronic intermittent cold stress and ketamine on reversal learning in females. Methods: Female Sprague-Dawley rats underwent 14 days of chronic intermittent cold and 3 days later received an injection of ketamine (10 mg/kg, i.p.). They were tested on reversal learning 24 hours post-injection. A separate cohort of female rats underwent 14 days of chronic intermittent cold. Three days later they received ketamine and were killed 2 hours post-injection for measurement of the synaptic marker PSD95 in orbitofrontal cortex. Results: Chronic intermittent cold induced a reversal learning deficit in females comparable with that seen in males, which was corrected by ketamine. Moreover, chronic intermittent cold increased PSD95 expression in orbitofrontal cortex, but this increase was not seen in rats receiving ketamine. Conclusions: Chronic intermittent cold stress and ketamine altered reversal learning in female rats similar to effects seen in males. Further, chronic intermittent cold increased PSD95 in orbitofrontal cortex of female rats, indicative of synaptic dysregulation. This effect was attenuated after ketamine administration.

Original languageEnglish (US)
Pages (from-to)1109-1113
Number of pages5
JournalInternational Journal of Neuropsychopharmacology
Volume21
Issue number12
DOIs
StatePublished - 2018

Keywords

  • Chronic stress
  • Cognitive flexibility
  • Females
  • Ketamine
  • Orbitofrontal cortex

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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