Elsevier

Biological Psychiatry

Volume 78, Issue 3, 1 August 2015, Pages 159-166
Biological Psychiatry

Priority Communication
Differences in Stress-Induced Changes in Extinction and Prefrontal Plasticity in Postweanling and Adult Animals

https://doi.org/10.1016/j.biopsych.2014.10.004Get rights and content

Abstract

Background

Postweaning is a critical developmental stage during which the medial prefrontal cortex (mPFC) undergoes major changes and the brain is vulnerable to the effects of stress. Surprisingly, the engagement of the mPFC in extinction of fear was reported to be identical in postweanling (PW) and adult animals. Here, we examined whether the effect of stress on extinction and mPFC plasticity would be similar in PW and adult animals.

Methods

PW and adult animals were fear conditioned and exposed to the elevated platform stress paradigm, and extinction and long-term potentiation were examined. The dependency of stress-induced modulation of extinction and plasticity on N-methyl-D-aspartate receptors was examined as well.

Results

We show that exposure to stress is associated with reduction of fear and enhanced induction of long-term potentiation (LTP) in PW pups, in contrast to its effects in adult animals. Furthermore, we report opposite effects in the occlusion of LTP following the enhanced or impaired extinction in the two age groups and that the reversal of the effects of stress is independent of N-methyl-D-aspartate receptor activation in PW animals.

Conclusions

Our results show that qualitatively different mechanisms control the modulatory effects of stress on extinction and plasticity in postweanling pups compared with adult rats. Our results point to significant differences between young and adult brains, which may have potential implications for the treatment of anxiety and stress disorders across development.

Section snippets

Methods and Materials

Adult (~60 days old) and postweanling (24–27 days old) male Sprague Dawley rats from the local animal colony at the Haifa University were used (for details, see Supplement 1).

Surgery and electrophysiological recordings were previously reported in our studies (39, 40) (Supplement 1).

Stress procedure was detailed elsewhere (39, 40) (Supplement 1). Corticosterone assessment is detailed in Supplement 1.

Detailed description of the procedure of fear conditioning and extinction was previously detailed

Effects of Exposure to Stress on Extinction in Adult and Postweanling Rats

Adult animals (adults, 60 days old) and postweanling pups (PW, 24–27 days old) were trained to associate a tone with an electrical footshock on the conditioning day. Twenty-four hours after conditioning, the animals were exposed to three tones for fear memory retrieval and immediately thereafter were either exposed to the elevated platform stressor (EP; adults-EP; n = 8; PW-EP; n = 7) or placed back in their home cage (adults-control; n = 8; PW-control; n = 8).

Two-way analysis of variance

Discussion

Using behavior, electrophysiology, and pharmacology, the major finding of this study is that following stress, the response profile of postweanling pups differs from that of the adult animal. However, it should be noted that baseline differences between the two age groups also exist, pointing to developmental differences that will be discussed in the next sections.

Acknowledgments and Disclosures

This project was supported by an Israel Science Foundation grant to MM (663/13). We thank Hamutal Rosengarten and Nissrin Lahoud for valuable help. The authors report no biomedical financial interests or potential conflicts of interest.

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