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

Background: Individuals with stress-related psychiatric disorders exhibit deficits in cognitive flexibility. We have shown that chronic intermittent cold (CIC) stress induces deficits in reversal learning, a form of cognitive flexibility mediated in the orbitofrontal cortex (OFC), that was reversed by ketamine in male rats. Such effects have not been tested in females. In this study, we examined effects of CIC stress and ketamine on reversal learning in females.

Methods: Female Sprague-Dawley rats underwent 14 days of CIC, and 3 days later received an injection of ketamine (10 mg/kg, i.p.). They were tested on reversal learning 24 hr post-injection. A separate cohort of female rats underwent 14 days of CIC. Three days later they received ketamine and were euthanized 2 hr post injection for measurement of the synaptic marker PSD95 in OFC.

Results: CIC induced a reversal learning deficit in females comparable to that seen in males, which was corrected by ketamine. Moreover, CIC increased PSD95 expression in OFC, but this increase was not seen in rats receiving ketamine.

Conclusions: CIC stress and ketamine altered reversal learning in female rats similar to effects seen in males. Further, CIC increased PSD95 in OFC of female rats, indicative of synaptic dysregulation. This effect was attenuated after ketamine administration.