Different effects of acute neonatal stressors and long-term postnatal handling on stress-induced changes in behavior and in ornithine decarboxylase activity of adult rats.

A transient increase in brain polyamine (PA) metabolism, termed the PA-stress-response (PSR), is a common response to stressful stimuli. Previous studies have implicated the PSR as a component of the adaptive and/or maladaptive brain response to stressful events. Ample evidence indicates that stressful experiences during early life can alter normal developmental processes and may result in pathophysiological and behavioral changes in the adult. The aim of the present study, therefore, was to determine whether strong acute neonatal stressors (3 mg/kg dexamethasone, or 2 h restraint stress at day 7), as compared to mild long-term intermittent maternal separation and handling (15 min, twice a day between postnatal days 2 and 25), would lead in adult Wistar rats to different PSR and behavioral reactivity to novelty stress. Changes in ornithine decarboxylase (ODC) activity and in tissue PA concentrations served as markers of the PSR, and behavioral alterations in an open-field arena indicated the reactivity to novelty stress. Animals subjected to acute neonatal stressors, showed reduced behavioral reactivity in the open-field test, indicative of increased emotional reactivity to novelty. In these animals, the increase in ODC activity after dexamethasone challenge was attenuated in the brain, but exaggerated in the liver. In the thymus and adrenal gland of these animals, the basal enzyme activity was significantly increased, but a similar reduction was observed after dexamethasone challenge. In contrast, long-term postnatal handling led in adults to novelty-induced changes indicative of reduced emotional behavior, yet the alterations in ODC activity after dexamethasone challenge in these animals were similar to those in animals after acute stressors. The concentrations of tissue polyamines in adults were not affected by any of the postnatal stressors. The results justify the following conclusions: (1) Strong acute neonatal stressors can lead to increased emotional behavior in adults, while mild long-term intermittent handling, may result in adaptation and reduced emotionality. (2) Attenuated stress-induced increase of ODC activity in the brain, but exaggerated increased activity in the liver, may be implicated in altered emotional behavior reactivity to stressors.

Developmental regulation of the brain polyamine-stress-response.

A transient increase in brain polyamine metabolism, termed the polyamine-stress-response is a common response to stressful stimuli. Previous studies have implicated an over-reactive polyamine response as a component of the maladaptive brain response to stressful events, and as a novel molecular mechanism involved in the pathophysiology of affective disorders. Ample evidence indicates that stressful experiences during early life can alter normal developmental processes and may result in pathophysiological and behavioral changes in the adult. Additionally, an important characteristic of affective disorders is their age dependency, a phenomenon that may be correlated with a maladaptive regulation of the hypothalamic-pituitary-adrenocortical (HPA) neuroendocrine system. In the present study we measured the activities of the enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase as markers of polyamine synthesis and found that unlike adults, immature rats do not show the characteristic brain polyamine-stress-response. Instead of the characteristic increase observed in adults, ornithine decarboxylase activity in immature animals was reduced or remained unchanged (for up to 16 days of age) after a dexamethasone injection or restraint stress application. The ontogenesis of this ornithine decarboxylase response was brain region-specific, indicating its dependence on the stage of neuronal maturation. Animals treated with dexamethasone at 7 days of age, showed increased behavioral reactivity in the open-field test as adults and an attenuated increase in ornithine decarboxylase activity after a re-challenge with dexamethasone at age 60 days. The results indicate that: (1) the brain polyamine-stress-response is developmentally regulated and its ontogenesis is brain region-specific, indicating dependence on the stage of neuronal maturation; (2) the switch to a mature polyamine-stress-response pattern coincides with the cessation of the stress hyporesponsive period in the HPA system: (3) activation of the polyamine-stress-response, as in the mature brain, appears to be a constructive reaction, while its down-regulation, as in the developing brain, may be implicated in neuronal cell death; (4) an attenuated dexamethasone-induced increase in ornithine decarboxylase activity implicates an altered polyamine-stress-response in the maladaptive response of the brain to stressful events.