Elevated Density of [³H]Imipramine Binding in Aged Human Brain

Abstract

Aging was associated with an increase in the density of specific binding sites for [3H]imipramine in postmortem specimens of human hypothalamus, frontal cortex, and parietal cortex. In general, [3H]imipramine binding was not affected by factors considered difficult to control in postmortem studies, i.e., time from death to autopsy and cause of death. The in vitro regulation of [3H]imipramine binding by sodium was impaired with age in hypothalamic homogenates. In vitro regulation of [3H]imipramine binding by chloride was intact. Determination of the concentrations of 5-hydroxytryptamine (serotonin) and 5-hydroxyindoleacetic acid in hypothalamus and frontal cortex indicated no apparent age-related changes in indole metabolism. The age-related increase in brain [3H]imipramine binding and impairment in the in vitro regulation of binding by ions are similar to changes observed previously in aged mouse brain. The increase in brain antidepressant binding sites is discussed in relationship to other indices of brain serotonergic function in aging and to the relationship of [3H]imipramine binding and depression.

Changes of lymphocyte beta‐adrenergic receptors and platelet serotonin reuptake sites in aging and dementias

“…It is interesting to note that similar results have been obtained in the cerebral cortex of aged animals (Brunello et al, 1988) and in the frontal cortex of aged volunteers (Severson et al, 1985). This further supports the hypothesis that circulating lymphocytes and platelets are a convenient tissue and a readily accessible model to study human neurotransmitter receptor systems since changes in these peripheral cells may reflect alterations in receptor responsiveness in a less accessible target tissue as the brain.…”

Age Stability of Human Brain 5-HT Terminals Studied with [³H]Paroxetine Binding

“…In contrast to the decrease in 5-HT-sensitive [3H]imipramine binding in the cingulate gyrus, the [3H]paroxetine binding was stable with age. In a study on desipramine-sensitive [3H]imipramine binding in human hypothalamus, an age-related increase was noted [2], However, this increase was likely to be explained by an increase in non specific binding [4], The present study, on the contrary, suggests and age-stability of the hy pothalamic 5-HT uptake sites.…”

“…In previous studies on the effect of aging of the 5-hydroxytryptamine (5-HT, serotonin) system, [3H]imipramine binding to the 5-HT uptake site has been used as an indirect marker for 5-HT terminals [1,2]. The initial data on desipramine-sensitive [3H]imipra-mine binding revealed age-related increases in binding density in frontal and parietal cor tices and in the hypothalamus [2].…”

“…The initial data on desipramine-sensitive [3H]imipra-mine binding revealed age-related increases in binding density in frontal and parietal cor tices and in the hypothalamus [2]. However, in a subsequent study, it was demonstrated that desipramine-sensitive [3H]imipramine binding contained a large fraction of nonspe cific binding [3], The increase in [3H]imipramine binding was rather an increase in non-specific binding [4].…”

Regional distribution of specific high affinity binding sites for 3H-imipramine and 3H-paroxetine in human brain

“…The comparison between 3H-imipramine and 3H-paroxetine binding to human brain has demonstrated that although it is possible to measure the neuronal serotonergic transport complex by the use of 3H-imipramine, (Langer et al, 1987;Severson et al, 1985;Raisman et al, 1979), paroxetine is a more specific inhibitor of serotonin uptake than imipramine, which may indicate that it is a better candidate for labelling the serotonin transport complex (Mellerup et al, 1986;Marcusson et al, 1988;Plenge et al, 1990;Hrdina, 1990a,b;Arranz et al, 1994).…”