Influence of aging and social isolation on changes in brain monoamine turnover and biosynthesis of rats elicited by novelty stress

Aging is a risk factor of human depression. Middle-aged or older men are vulnerable to adverse life events and an absence of social contact and easily become depressed. In the present study, we investigated the influence of aging on responses to life events in socially isolated conditions. We applied isolation-rearing (4 W) to two age groups, older (18 M) and younger (11 W), of male F344 rats that had been reared in a group and then examined responses to novelty stress (20 min). Changes in brain monoamines and their metabolites such as dopamine (DA), serotonin (5-HT), dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in six regions: the prefrontal cortex, nucleus accumbens, hippocampus, amygdala, midbrain, and raphe nuclei. MANOVA was carried out for rearing condition, age, and novelty stress. Isolation significantly changed monoamines and their metabolites, except in amygdala and raphe nuclei. Aging significantly altered them in all regions, although novelty stress did not. In the amygdala and midbrain, isolation significantly changed monoamine biosynthesis, with monoamine turnover remaining unchanged. In the prefrontal cortex and nucleus accumbens, aging significantly altered turnover, while biosynthesis remained unchanged. Novelty stress significantly varied only the turnover in the prefrontal cortex. The interaction between isolation and aging indicated that aging influences changes in turnover and biosynthesis elicited by isolation primarily at the center of the mesolymbic DA system, the midbrain, and in raphe nuclei of the 5-HT system. In peripheral regions of the mesolymbic system, aging primarily affects changes in turnover induced by isolation.