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Int J Neurosci. 2019 Jan;129(1):1-9. doi: 10.1080/00207454.2018.1501049. Epub 2018 Aug 31.

Spontaneous recovery of fear differs among early - late adolescent and adult male mice.

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a Center for Medical Sciences , Ibaraki Prefectural University of Health Sciences , Ibaraki , Japan.
b Department of Cognitive Behavioral Physiology , Chiba University Graduate School of Medicine , Chiba , Japan.
c Research Center for Child Mental Development , Chiba University Graduate School of Medicine , Chiba , Japan.
d Department of Pharmacotherapeutics , Showa Pharmaceutical University , Tokyo , Japan.
e Department of Ultrastructural Research , National Institute of Neuroscience, National Center of Neurology and Psychiatry , Tokyo , Japan.


Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA.


Erk; Fear conditioning; age difference; fear extinction; spontaneous recovery of fear

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