The effect of temporary amygdala inactivation on extinction and reextinction of fear in the developing rat: unlearning as a potential mechanism for extinction early in development.

It is well accepted that fear extinction does not cause erasure of the original conditioned stimulus (CS)-unconditioned stimulus association in the adult rat because the extinguished fear often returns (e.g., renewal and reinstatement). Furthermore, extinction is NMDA and GABA dependent, showing that extinction involves new inhibitory learning. We have recently observed each of these extinction-related phenomena in 24-d-old but not in 17-d-old rats. These results suggest that different neural processes mediate extinction early in development. However, the neural processes underlying extinction in the developing rat are unknown. Therefore, the present study investigated amygdala involvement in extinction and reextinction during development. In experiment 1, temporary inactivation of the amygdala (using bupivacaine, a sodium channel modulator) during extinction training impaired extinction of conditioned fear in 17- and 24-d-old rats. In experiment 2, 17- and 24-d-old rats were conditioned, extinguished, and then reconditioned to the same CS. After reconditioning, the CS was reextinguished; at this time, some rats at each age had their amygdala temporarily inactivated. Reextinction was amygdala independent in 24-d-old rats, as previously shown in adult rats. However, reextinction was still amygdala dependent in 17-d-old rats. In Experiment 3, the age at conditioning, reconditioning, reextinction, and test was held constant, but the age of initial extinction varied across groups; reextinction was found to be amygdala independent if initial extinction occurred at 24 d of age but amygdala dependent if it occurred at 17 d of age. Consistent with previous findings, these results show that there are fundamental differences in the neural mechanisms of fear extinction across development.