The effect of antidepressants on rodent brain glucocorticoid systems

Maurya, Manisha (2001). The effect of antidepressants on rodent brain glucocorticoid systems. PhD thesis The Open University.



The aetiology of depression and mechanisms of action of antidepressant drugs continue to be evasive. Evidence suggests that alterations in brain corticosteroid receptors may be a crucial factor in these events. Previous measurements of corticosteroid receptors (CR) and CR mRNA in animal tissues following stress and/or antidepressant administration have not attempted to measure CR in intact animals using different antidepressants, in various tissues or in putative animal models of stress.

The following investigations were aimed at quantifying CR and plasma corticosterone concentrations using radioligand binding and high performance liquid chromatography or radio-immunoassays, respectively. Behavioural investigations conducted in animal models of stress were extended to study the effects of antidepressants.

Antidepressant administration to intact animals had various effects. Cortical CR were increased after 14 days of DMI; paroxetine induced a reduction in cortical CR after 14 days; no changes were observed following venlafaxine for up to 28 days. There were no significant changes in CR binding parameters in the hippocampus, striatum or hypothalamus following antidepressant administration. CR in the thymus were reduced following paroxetine.

No significant effects of olfactory bulbectomy or antidepressant administration were observed on CR binding parameters. However, significant increases in locomotor activity were observed in bulbectomised rats, which were attenuated by chronic, antidepressant treatment.

In a putative stress model involving chronic exposure of mice to predator odour, no significant effects were observed on locomotor activity following predator exposure and/or antidepressant administration. Sucrose intake was decreased, representing a possible anhedonic response to chronic predator stress. Predator stress and/or antidepressant administration had no significant effects on cortical or hippocampal CR binding or plasma corticosterone concentrations.

The results of these investigations demonstrate that CR alterations observed in stress/depression are not reflected in the chosen animal models. CR changes following chronic antidepressant administration, though forming part of a biochemical cascade, are not likely to constitute a common mechanism of action for antidepressant drugs.

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