Juvenile stress alters the prefrontal synaptic response during fear extinction

Objectives: Stress-related disorders including phobic anxiety disorders are common problems in dental treatment. To elucidate the neural mechanisms in phobic anxiety disorders such as “dental phobia”, the effect of early postnatal stress on the neuronal regulation in the medial prefrontal cortex (mPFC) during context-dependent fear extinction was examined under consciousness. Methods: Male Wistar rats were divided into three groups, i.e., 3W-FS (n=6); rats exposed to footshock (FS; 0.5 mA, 2 s/30sec, 5 times) at the postnatal day (PND) 21 to 25 (week 3), 2W-FS (n=6); rats exposed to FS at PND 14-18, and non-FS control (n=6). In the postadolescent period, they were recorded their population spike amplitude (PSA) in the mPFC during context-dependent fear extinction trials. Statistical analysis of the data was performed using one way ANOVA followed by Dunnett's post hoc test. Results: Compared to controls, 3W-FS group had significantly impaired extinction of contextual fear-related behavior (p<0.05). In the extinction session, the recovery of the inhibitory synaptic response in the mPFC observed in controls was attenuated in 3W-FS. The neuronal and behavioral deficits observed in 3W-FS were significantly restored by single treatment with the 5-HT_1A receptor agonist tandospirone (1 mg/kg, i.p.) (p<0.05). Conclusion: The present findings suggest that early postnatal stress affects the neural circuit responsible for the extinction of context-dependent fear memory, which may be involved in serotonergic mechanism(s) mediated via 5-HT_1A receptors.