BLOCKADE OF CORTICOSTERONE SYNTHESIS REDUCES SEROTONIN TURNOVER IN THE DORSAL HIPPOCAMPUS OF THE RAT AS MEASURED BY MICRODIALYSIS

The influence of plasma corticosterone concentration on serotonin (5-H T) turnover in the dorsal hippocampus was investigated, The experiment s were performed in freely moving male Wistar rats in their home cage. Blood samples were taken via a permanent jugular Vein catheter to det ermine plasma corticosterone levels. Extracellular levels of 5-HT and its metabolite 5-hydroxy-indole acetic acid (5-HIAA) were measured usi ng in vivo microdialysis. The rats received an intravenous (i.v.) infu sion of the steroid synthesis-inhibitor metyrapone (150 mg/kg/ml) in o rder to manipulate circulating corticosterone levels. Three hours late r, the monoamine oxidase inhibitor pargyline (15 mg/kg/2 ml i.v.) was administered to produce an accumulation of extracellular 5-HT. Pargyli ne administration led to a four fold increase in 5-HT levels, while re ducing 5-HIAA by 45%. Metyrapone pretreatment blocked the pargyline-in duced rise in plasma corticosterone to baseline levels and diminished the pargyline-induced increase in 5-HT, without affecting 5-HIAA level s, Thus, the data suggest that a decrease in availability of corticost erone for its receptors by metyrapone diminished the 5-HT synthesis ra te. Since plasma corticosterone levels during this blockade are still low, it is assumed that brain glucocorticoid receptor occupation is re duced, while mineralocorticoid receptors are still substantially occup ied. Therefore the present results support the hypothesis that cortico sterone through glucocorticoid receptor activation enhances 5-HT synth esis rate and release in the dorsal hippocampus.