Effects of single-dose ketamine infusion on behavioral parameters and neuronal activation in the medial prefrontal cortex of juvenile rats exposed to prenatal stress

Objectives: Subanesthetic dose of ketamine administration produces antidepressant-like response especially in treatmentresistant depression patients. Ketamine’s rapid and sustained actions have also been demonstrated in normal or chronically stressed animals, but no experimental studies have examined its effects in prenatally stressed rodents. Therefore, aim of the present study was to investigate the behavioral and structural consequences of single-dose ketamine application in juvenile rats exposed to prenatal stress. Methods: Prenatal stress protocol was applied by immobilization of pregnant rats during the last week of their gestation for 3 hours a day. While treatment group received a single-dose (10 mg/kg) of intraperitoneal ketamine injection, control and stress groups received same amount of saline injections at P38. After completion of behavioral tests (sucrose preference, modified grip and forced swim), animals were sacrificed via intracardiac perfusion. Then, immediate gene expression in the medial prefrontal cortex was evaluated by c-Fos immunohistochemistry. Results: Although the active coping and depressive-like behavior of juvenile animals exposed to prenatal stress did not significantly change, ketamine application caused alterations in the sucrose preference pattern of animals and immobility time in the forced swim test. Two-way ANOVA test results showed significant differences among groups and a group X gender interaction in the density of c-Fos expressing neurons present in the medial prefrontal cortex. Conclusion: A single-dose ketamine treatment might differentially affect the depressive-like behaviors of juvenile animals exposed to prenatal stress and activate neurons in the medial prefrontal cortical region in a gender-dependent manner. Keywords: c-Fos; depression; ketamine; prefrontal cortex; prenatal stress