Early-life stress and the persistence of fear in rats

Abstract

This thesis investigated the effect of early-life exposure to stress or corticosterone on fear retention and extinction across two generations of infant rats. In the first series of experiments rats were exposed to maternal-separation (MS) or standard-rearing (SR) from postnatal day (P) 2-14 before being assessed for fear retention (Chapter 2) and extinction (Chapter 3). In all experiments fear conditioning took place on P17. While SR rats exhibited typical infant memory, showing nearly complete forgetting of a fear association within a week, MS rats behaved more like adults and remembered a fear association for 30 days post-training. Infant SR rats also exhibited a form of extinction learning which was resistant to relapse and the extinguished fear memory was not recovered by a pre-test injection of FG7142 in those rats. On the other hand, MS rats showed relapse after extinction and a pre-test injection of FG7142 recovered the extinguished fear response in these rats. Taken together, these experiments provide strong evidence that MS led to an early transition between infant and adult-like fear retention and extinction systems. The second series of experiments (Chapter 4) examined whether the stress hormone corticosterone, administered either to the mother or directly to the pups, could mimic the effects of MS on infant fear retention and extinction. Corticosterone administered through either method led to an early transition between the infant and adult-like fear retention and extinction systems. The third and final series of experiments (Chapter 5) examined whether the early transition in fear retention and extinction systems was also apparent in the first generation offspring of male rats that had been exposed to MS (MS-F1) or SR (SR-F1). While SR-F1 rats exhibited typical infant fear retention and extinction behaviour (i.e., rapid forgetting and no relapse after extinction), MS-F1 rats exhibited better fear retention and showed some relapse after extinction, suggesting that the early transition in fear retention and extinction systems is also seen in the next generation. The implications of these findings are discussed in light of current theoretical and neural models of fear retention and extinction.