Decreased Brain Serotonin Turnover after Short Term (Two-Hour) Adrenalectomy in Rats: A Comparison of Four Turnover Methods*

Abstract

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.

Mineralocorticoid and glucocorticoid receptors in the brain. Implications for ion permeability and transmitter systems

“…In agreement with this are data showing that shortly (1-2 hr) after ADX, 5HT turnover is reduced in the hypothalamus, midbrain and hippocampus; treatment with low doses of corticosterone administered at the time of ADX restores the 5HT turnover (Van Loon et al, 1981;de Kloet et al, 1982de Kloet et al, , 1983. While in one study (Van Loon et al, 1981) dexamethasone was also able to restore the ADX-induced changes of 5HT turnover, we observed that only low doses of corticosterone and not dexamethasone or aldosterone given at the time of ADX were able to restore the reduced 5HT synthesis rate in the raphe area and the dorsal hippocampus 1 hr after the stressful surgical procedure (de Kloet et al, 1982(de Kloet et al, , 1983. In fact, dexamethasone treatment after ADX even further reduced the 5HT turnover, and pretreatment 1 hr before ADX with dexamethasone or aldosterone prevented, in the raphe-hippocampal system, the reduction of 5HT turnover due to ADX.…”

Regional Serotonin Metabolism under Basal and Restraint Stress Conditions in the Brain of Transgenic Mice with Impaired Glucocorticoid Receptor Function

“…Decreases in 5-HT synthesis and turnover were reported in various brain areas of ADX rats [3, 4, 5, 29]. Therefore, we hypothesized that 5-HT metabolism would be affected in TG mice presenting alterations of the HPA axis functioning.…”

“…Data related to the influence of corticosteroids upon basal 5-HT metabolism or 5-HT 1A autoreceptors involved in the regulation of 5-HT metabolism in the brain stem are contradictory [2, 3, 30, 31, 32]. Moreover, since 5-HT turnover was found to be decreased in the pons medulla but not in the midbrain area including the rostral pons after short-term ADX [5], the absence of difference in basal 5-HT metabolism in the brain stem between control and TG mice might result from the fact that our dissection includes all raphe nuclei and the surrounding area so that a region-specific effect might have been blunted.…”

“…Although some authors reported no change in indices of the basal metabolism of serotonin (5-hydroxytryptamine, 5-HT) in the hippocampus, cortex or striatum after adrenalectomy (ADX) [1, 2], others, using different recovery periods after surgery, showed that removal of corticosterone reduces indices of basal 5-HT synthesis and turnover in the brain stem where the raphe nuclei which contain the serotoninergic cell bodies are located and also in the hippocampus and hypothalamus [3, 4, 5]. Moreover, many studies reported that basal circulating corticosterone levels exert inhibitory effects on mRNA expression and/or binding characteristics and functions of 5-HT 1A , 5-HT 1B and 5-HT 2C receptors, particularly in the hippocampus, and some of these effects could be the consequence of corticosterone-induced changes in 5-HT turnover [6, 7].…”

Regulation of Hippocampal 5-HT1A Receptor Gene Expression by Dexamethasone

“…Animal studies have shown that corticosteroids can alter several elements of serotonergic neurotransmis sion, including serotonin (5-HT) metabolism and turn over (Curzon et al 1972;Van Loon et al 1981;Singh et al 1990). However, it is also evident that adrenal steroids can act to directly regulate 5-HT receptors (Bie gon et al 1985;De Kloet et al 1986), providing a direct means by which corticosteroids can act to modulate syn aptic serotonergic activity.…”