engleski

The effect of acute and short-term administration of desipramine on the 5-HT synthesis rate in the rat brain: an autoradiographic study

The rate of serotonin (5-HT) synthesis was measured in the discrete rat brain regions, using an original autoradiographic method (Diksic et al., J. Cereb. Blood Flow Metab., 10:1-12, 1990), after an administration of desipramine, a classic antidepressant and noradrenaline uptake blocker. The opposite, time-dependent effects of an acute and short-term treatment with desipramine (10 mg/kg, i.p.) on the 5-HT synthesis rate were found. In all treatments desipramine did not affect plasma tryptophan concentration. Acute desipramine, injected 2 h before i.v. infusion of 14-C-alpha-methyltryptophan, significantly decreased the 5-HT synthesis rate in the areas of serotoninergic cell bodies (i.e. raphe nuclei), but increased it in regions of the serotoninergic terminals (cortices, caudate, globus pallidus). On the other hand, short-term (7 days) desipramine treatment (the last dose given 24 h before tracer) increased 5-HT synthesis rate in dorsal raphe, but decreased it in some regions containing serotoninergic terminals like caudate, auditory cortex, superior and inferior colliculus, superior olive. These data suggest that noradrenaline is involved in the regulation of 5-HT synthesis rate in the discrete rat brain regions. It seems that desipramine affects 5-HT synthesis in rat brain differently when given acutely or chronically. Supported by the MRC of Canada (MA 10232), US Public Service (RO1-NS29629), and Croatian Ministry of Science.

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