Extinction of conditioned fear in the developing rat

Abstract

The present thesis examined extinction of conditioned fear in the developing rat. In the adult rat, the hippocampus is thought to be important for the context-specificity of extinction. Because the hippocampus is a late-maturing structure, it was hypothesised that context-modulation of extinction may be different across development. The first series of experiments investigated reinstatement of extinguished fear in the developing rat (Chapter 2). The results showed that P24 rats exhibited context-specific reinstatement. On the other hand, P17 rats did not exhibit reinstatement of extinguished fear following a US reminder treatment. The failure to see reinstatement in P17 rats was not due to the reminder treatment being ineffective in these rats because the same treatment alleviated spontaneous forgetting in rat this age. The second series of experiments then examined the renewal effect and GABAergic involvement in extinction in P24 and P17 rats (Chapter 3). It was observed that P24 rats displayed renewal whereas P17 rats did not. Also, pre-test injection of FG7142 recovered extinguished fear in P24 rats but not in P17 rats, even across a range of doses. This failure to see any FG7142 effect on extinction in P17 rats was not due to the lack of responsiveness to this drug in these rats because FG7142 was found to be effective in alleviating spontaneous forgetting in rats this age. The third series of experiments then examined the effect of temporary inactivation of the amygdala on extinction and re-extinction in the developing rat (Chapter 4). It was observed that extinction retention is impaired in both P24 and P17 rats if the amygdala is inactivated during extinction training. Interestingly, when a CS that had been previously extinguished and then re-trained was re-extinguished, re-extinction was amygdala-independent if initial extinction occurred at 24 days of age but amygdala-dependent if initial extinction occurred at 17 days of age. That is, amygdala involvement in re-extinction was dissociated across development. Taken together, these experiments provide strong evidence for fundamental differences in mechanisms underlying fear extinction across development. The implications of the findings were discussed in light of the theoretical and neural models of extinction.