[Long-lasting sensitization to footshock after chronic variable stress on the acoustic startle reflex]

Corticotropin releasing hormone (CRH)--and norepinephrine (NE) -containing neurons in the brain are activated during stress. We previously reported a decrease in the basal level of CRH immunoreactivity in the central nucleus of the amygdala and the tyrosine hydroxylase immunoreactivity in the locus coeruleus after chronic variable stress (CVS), whereas both responses were augmented by a novel stress (footshock). Since the acoustic startle reflex (ASR) can be enhanced by the CRH neuronal activity in the central nucleus of the amygdala, we examined the influence of footshock on ASR in rats exposed to CVS. The footshock after CVS caused a significant augmentation of ASR compared with the acute footshock. Moreover, the enhanced startle to acute footshock was maximally increased at 6 min and was absent after 40 min, whereas the maximal change of the enhanced startle to footshock after CVS was delayed to 14 min and the significant enhanced startle was found until 180 min. The footshock-enhanced startle after CVS may be related to the augmentation of CRH-NE activity, leading to the possibility that a prolonged CRH hyperactivity to stress might generate a pathophysiology of major depression with a vulnerability to stress.