Ketamine prevents stress-induced cognitive inflexibility in rats.
Chronic stress produces both morphological and functional alternations of the rat medial prefrontal cortex (mPFC). N-methyl-d-aspartic acid (NMDA) glutamate receptor inhibition may alleviate such stress-induced dendritic reorganization in the mPFC. However, it is unknown whether administration of a NMDAR antagonist would also prevent alterations in PFC-mediated cognitive functions. Here, we investigated whether administration of ketamine, the noncompetitive antagonist of NMDA receptors before each stress session would prevent cognitive impairments in a rat model of prefrontal cortex (PFC)-dependent attentional set-shifting task (ASST), a measure of cognitive flexibility. Repeated restraint stress (1h daily for 7 days) significantly and specifically impaired extra-dimensional (ED) set-shifting ability of rats. Pretreatment with ketamine (10mg/kg, IP) completely and specifically prevented this stress-induced cognitive inflexibility. The present study demonstrates procognitive efficacy of ketamine in an animal stress model, which confirms and extends the role of the NMDA receptors in mediating stress-evoked prefrontal dysfunctions.
Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Agnieszka
A
Nikiforuk
Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: nikifor@if-pan.krakow.pl.
Piotr
P
Popik
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000209:etiology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000523:psychology; D013315:Stress, Psychological / Q000523:psychology*
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine
Cognitive deficit; Ketamine; NMDA receptors; Prefrontal cortex; Set-shifting; Stress