Decreased brain serotonin turnover after short term (two-hour) adrenalectomy in rats: a comparison of four turnover methods.

Within the first 2 h after adrenalectomy in rats there is a marked decrease in hypothalamic, brain stem, and hippocampal serotonin (5HT) turnover. This adrenalectomy-induced decrease in brain 5HT turnover was demonstrated in this study using four different methods. These include 1) accumulation of 5HT after monoamine oxidase inhibition with pargyline, 2) decline of 5-hydroxyindoleacetic acid after pargyline, 3) accumulation of 5-hydroxytryptophan after aromatic L-amino acid decarboxylase inhibition with m-hydroxybenzylhydrazine, and 4) accumulation of 5-hydroxyindoleacetic acid after probenecid. The adrenalectomy-induced decreases in 5HT turnover in these areas were prevented by glucocorticoid treatment with either corticosterone or dexamethasone. The similarity of the results obtained with four different methods of assessment of brain 5HT turnover provides strong evidence to suggest that the activity of 5HT neurons, in at least three brain areas, is decreased within the first 2 h after adrenalectomy. Also, it seems likely that glucocorticoid withdrawal is the important factor in this adrenalectomy-induced decrease in brain 5HT turnover. In addition, an increase in hypothalamic 5HT turnover in response to the surgical stress of sham adrenalectomy could be demonstrated. The adrenalectomy-induced decreases in brain 5HT turnover were also prevented by the administration of the serotonin receptor antagonist, pizotifen. In addition, serotonin receptor blockade with pizotifen inhibited the effect of corticosterone to normalize the adrenalectomy-induced changes in both the plasma ACTH concentration and brain 5HT turnover. These data provide further support for an interaction between glucocorticoids and brain 5HT neurons.