Reproductive experience alters the involvement of N-methyl-D-aspartate receptors in fear extinction, but not fear conditioning, in female Sprague Dawley rats

Abstract

Recently, evidence has emerged showing that the behavioural and hormonal features of fear extinction are altered as a result of reproductive experience in both rats and humans. The current set of experiments sought to determine whether reproductive experience also alters the molecular features of fear extinction. In adult male rats, it has been widely demonstrated that the activation of N-methyl-d-aspartate receptors (NMDAR) is essential for fear extinction. We therefore compared the involvement of NMDAR in fear extinction between nulliparous (virgin) and primiparous (reproductively experienced) female rats. Nulliparous and primiparous females received systemic administrations of either MK-801 (a non-competitive NMDAR antagonist) or saline prior to extinction training. MK-801 was found to impair extinction recall in nulliparous females, but not primiparous females. When the same dose of MK-801 was administered prior to conditioning, both groups of rats showed impaired recall of conditioning the following day. The results of these experiments indicate that the extinction, but not the acquisition of fear, may become NMDAR-independent following reproductive experience.