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 dis-playing depressive-like behavior following chronic stress exposure, glutamatergic transmission increases in the NAc. NMDAreceptor antagonist ketamine act as an antidepressant, especially in treatment-resistant cases. In this study, we aimed toinvestigate 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. Maleoffspring were divided into four groups at postnatal day 40. Prenatal stress and control groups received either a single dose ofketamine (10 mg/kg, i.p.) or same doses of saline injections. Immediate gene activation was stimulated by forced swim for 6minutes and assessed by c-Fos immunohistochemistry. The total number of activated cells in the core and shell subregions wasestimated by optical fractionator method. Results: The total number of activated cells in the shell subregion significantly decreased in prenatally stressed rats. Ketamineadministration reversed their activation level similar to those of control group. Although activation of cells did not change in thecore region following prenatal stress, ketamine treatment enhanced the activation of cells in this region both control and pre-natally stressed animals. Conclusion:These results suggest that prenatal stress influences the activation of NAc in a subdivision specific manner, butketamine treatment could act on both core and shell regions by affecting glutamatergic limbic information that flows fromshell to core subregion of the NAc.