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

Abstract

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.

Exacerbated loss of cell survival, neuropeptide Y‐immunoreactive (IR) cells, and serotonin‐IR fiber lengths in the dorsal hippocampus of the aged flinders sensitive line “depressed” rat: Implications for the pathophysiology of depression?

“…Whether a maintained number of 5-HT-IR cells in the dorsal raphé nucleus of FSL rats reflects a compensatory mechanism to counteract a possible age-related impairment of hippocampal 5-HT innervation is a matter of speculation, but it remains a heuristic possibility. Although agingassociated impairments in the serotonergic system have been reported for normal rats in several studies (Davidoff and Lolova, 1991;Maines et al, 1998;Miura et al, 2002), our results suggest that earlier and more pronounced alterations in the 5-HT system may take place in individuals with a genetic predisposition to depression.…”

The international society for developmental psychobiology annual meeting symposium: Impact of early life experiences on brain and behavioral development

“…A variety of studies have revealed that the activation of the HPA-axis, as it occurs, for instance, during the separation from the mother or both parents (Gruss, Westphal, Luley, & Braun, 2006;Lehmann & Feldon, 2000) and other juvenile and adult stress paradigms (Kudielka & Kirschbaum, 2005), modulate monoaminergic systems in adult animals (Fuchs & Flugge, 2002) and also during development. For instance, rats which have been raised in social isolation display dramatically decreased dopamine metabolites (Miura, Qiao, & Ohta, 2002). This is in line with anatomical findings in degus and gerbils which were raised under socially deprived conditions and which as adolescents showed reduced densities of dopaminergic fiber innervation in some subregions of the prefrontal cortex (Braun, Lange, Metzger, & Poeggel, 2000;Winterfeld, Teuchert-Noodt, & Dawirs, 1998).…”

Differential neuronal changes in medial prefrontal cortex, basolateral amygdala and nucleus accumbens after postweaning social isolation

“…In the present study, the basal DA levels in male Wistar rats isolated from P28 to P85 are not different from age-matched group-reared controls. Unlike a great number of studies focusing on DA levels in the mPFC and NAc, relatively fewer works address the change of DA level in the AMY in social isolation model (Heidbreder et al 2000;Miura et al 2002). In isolationreared male Wistar rats (isolated from P21 to P105), the DA level in the AMY is reduced, yet the DA turnover is increased (Heidbreder et al 2000).…”