The Antidepressant-Like Effects of a Clinically Relevant Dose of Ketamine Are Accompanied by Biphasic Alterations in Working Memory in the Wistar Kyoto Rat Model of Depression
Frontiers in Psychiatry January 20, 2021 Conor McDonnell, F. Dunphy-Doherty, J. Rouine et al.
Ketamine rapidly and lastingly reverses depressive-like behaviors in Wistar Kyoto rats, a strain that models treatment-resistant depression, but also causes transient side effects. WKY rats showed increased immobility, reduced activity, anhedonia, and working memory deficits compared to Sprague Dawley rats. A single 5 mg/kg dose of ketamine, matching clinical plasma exposure, rescued these behaviors. The same dose temporarily decreased locomotor activity and positive vocalizations, acutely impaired working memory, yet later improved cognition. These findings support the WKY rat as a translational model for testing new rapid-acting antidepressants.