Evidence that a single exposure to aversive stimuli triggers long-lasting effects in the hypothalamus-pituitary-adrenal axis that consolidate with time

Abstract

Because of its use as a negative reinforcer in animal studies and its potential pathological impact (e.g. post-traumatic stress disorder and depression), exposure to aversive stimuli is a relevant model for studying CNS plasticity. We present evidence that a single exposure to two predominantly emotional stressors [restraint in tubes and immobilization on wooden boards (IMO)] can modify the response of the hypothalamo-pituitary-adrenal (HPA) axis to a subsequent exposure to the same stressor days later in that a more rapid return to the baseline was observed in the poststress period. In addition, the effect was greater with IMO, the more severe stressor. Using IMO, we have further demonstrated that the effect of a previous single exposure to the stressor (i) increased with days elapsed between the two exposures; (ii) was specific for the previously experienced stressor; and (iii) was mediated via central-mediated effects [corticotropin-releasing factor (CRF) mRNA in the paraventricular nucleus of the hypothalamus]. These data suggest that animals retain memory about a single experience with stressors, resulting in an acceleration of the poststress recovery of the HPA axis that enhances progressively over a period of weeks. The extent to which the present data are relevant regarding post-traumatic stress disorders is unclear, but the study of the HPA response to severe stressors may be suitable for the study of the neurobiological basis of the progressive consolidation of learning over a long period of time (days to weeks).