, Volume 236, Issue 1, pp 251–264 | Cite as

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

  • Samantha TangEmail author
  • Bronwyn M. Graham
Original Investigation


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.


Anxiety disorders Fear extinction Fear conditioning NMDA receptors Reproductive experience 



This work was supported by grants from the Australian Research Council (DE140100243 and DP180101563) to BMG and an Australian Postgraduate Award to ST.

Compliance with ethical standards

All rats were treated according to The Australian Code of Practice for the Care and Use of Animals for Scientific Purposes (8th edition), and all procedures were approved by the Animal Care and Ethics Committee at The University of New South Wales.

Conflicts of interest

The authors declare that they have no conflict of interest.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of PsychologyUNSWSydneyAustralia

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