Norepinephrine mediates contextual fear learning and hippocampal pCREB in juvenile rats exposed to predator odor

Predator odors induce unconditioned fear in the young animal and provide the opportunity to study the mechanisms underlying unlearned and learned fear. In the current study, cat odor produced unlearned, innate fear in infant (postnatal age 14; PN14) and juvenile (PN26) rats, but contextual fear learning occurred only in juveniles. It was hypothesized that contextual fear learning in juveniles is mediated by norepinephrine. Consistent with this hypothesis, pre-training injection of the β-adrenergic antagonist propranolol reduced the unlearned fear response while post-training injection inhibited contextual fear learning in juvenile rats exposed to cat odor. We suggest that NE mediates the formation of contextual fear memories by activation of the transcription factor CREB in the hippocampus in juveniles but not in infants. Levels of phosphorylated CREB (pCREB) were increased in the dorsal and ventral hippocampi of juvenile rats exposed to cat odor. These levels were not increased in infants or juveniles exposed to a control odor. Further, propranolol blocked these increases in pCREB. In conclusion, although innate fear occurs within the neonatal period, contextual fear learning is a relatively late-occurring event, is hippocampal dependent, and mediated by norepinephrine.