The Imipramine Binding Site: Effects of Aging, Ovarian Hormones, Adrenal Hormones, and Chronic Antidepressant Treatment
Wilson, Marlene Ann
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Permalink
https://hdl.handle.net/2142/77679
Description
Title
The Imipramine Binding Site: Effects of Aging, Ovarian Hormones, Adrenal Hormones, and Chronic Antidepressant Treatment
Author(s)
Wilson, Marlene Ann
Issue Date
1985
Department of Study
Neuroscience
Discipline
Neuroscience
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Neuroscience
Language
eng
Abstract
Binding sites for the antidepressant imipramine have been described in the brain and blood platelets of several species of animals, including rats and humans. Decreased levels of imipramine binding sites are found in depressed patients when compared to controls.
Based on the therapeutic time lag of clinical antidepressant therapy, animal studies have mainly examined the effects of chronic antidepressant treatment on imipramine binding sites. We have found that age alters the observed response of imipramine binding sites to chronic imipramine treatment in female rats. These apparent changes in the imipramine binding site response are the result of age-related differences in the metabolism of imipramine, which lead to an enhanced accumulation of imipramine metabolites in older females. Imipramine binding sites are thought to modulate the presynaptic re-uptake site for the neurotransmitter serotonin. We have examined whether the effects of age and chronic antidepressant treatment on imipramine binding sites are associated with changes in serotonin reuptake by measuring both parameters in the same membrane preparation. The results indicate a positive correlation between imipramine binding sites and serotonin re-uptake in the hypothalamus, suggesting that changes in imipramine binding may modulate serotonergic activity.
We have examined the influences of age, gender, ovarian hormones and adrenal hormones on serotonergic systems as evidenced by their ability to modulate imipramine binding sites in the hypothalamus of rats. These factors also seem to play some role in the etiology of depressive disorders. Imipramine binding sites increase in concentration but decrease in affinity as female rats age. Ovarian hormones can modify imipramine binding sites of rats as demonstrated by the higher imipramine binding concentration in females having high estrogen levels than females with low estrogen. Females also show higher levels of hypothalamic imipramine binding sites than male rats of comparable age. Finally, analysis of adrenalectomized and control animals throughout the lighting cycle indicated that imipramine binding sites vary diurnally in both control and adrenalectomized female rats. Although adrenalectomy failed to significantly alter imipramine binding sites, the data suggested that adrenalectomy may modulate imipramine binding sites at certain times of day.
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