Single dose ketamine injection affects activation of cells in the nucleus accumbens of prenatally stressed rats

Abstract

Objectives: The nucleus accumbens (NAc) has recently been implicated in the pathophysiology of depression. In animals displaying depressive-like behavior following chronic stress exposure, glutamatergic transmission increases in the NAc. NMDA receptor antagonist ketamine act as an antidepressant, especially in treatment-resistant cases. In this study, we aimed to investigate the effects of single-dose ketamine application in the activation of cells in the NAc of prenatally stressed rats. Methods: Sprague-Dawley dams were exposed to immobilization stress during the last week of pregnancy for 3 hours. Male offspring were divided into four groups at postnatal day 40. Prenatal stress and control groups received either a single dose of ketamine (10 mg/kg, i.p.) or same doses of saline injections. Immediate gene activation was stimulated by forced swim for 6 minutes and assessed by c-Fos immunohistochemistry. The total number of activated cells in the core and shell subregions was estimated by optical fractionator method. Results: The total number of activated cells in the shell subregion significantly decreased in prenatally stressed rats. Ketamine administration reversed their activation level similar to those of control group. Although activation of cells did not change in the core region following prenatal stress, ketamine treatment enhanced the activation of cells in this region both control and prenatally stressed animals. Conclusion: These results suggest that prenatal stress influences the activation of NAc in a subdivision specific manner, but ketamine treatment could act on both core and shell regions by affecting glutamatergic limbic information that flows from shell to core subregion of the NAc.