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Effect of monoamine oxidase A and B inhibition on the uptake and metabolism of serotonin within serotonergic neurons of rat brain

Department of Pharmacology and Psychiatry, Southern Illinois University School of Medicine, Springfield, Illinois, USA

R.E. Becker

Department of Pharmacology and Psychiatry, Southern Illinois University School of Medicine, Springfield, Illinois, USA

The effects of inhibiting monoamine oxidase (MAO) A and B on metabolism and uptake of serotonin (5-HT) in serotonergic synaptosomes were studied. To avoid contamination by extrasynaptosomal MAO, synaptosomes were separated from other components of rat brains by discontinuous sucrose density gradient centrifugation. Kinetic analysis of 5-HT uptake demonstrated that 5-HT was selectively transported into serotonergic synaptosomes through the high affinity 5-HT uptake process. Selectivity of the uptake and subsequent deamination of 5-HT within serotonergic synaptosomes were confirmed using selective and non-selective 5-HT and norepinephrine (NE) uptake inhibitors. MAO inhibitor analysis of 5-HT deamination occurring within serotonergic synaptosomes indicated that, at physiologically relevant concentrations of 5-HT, MAO A deaminates 5-HT, maintaining a low cytoplasmic concentration of 5-HT. When the cytoplasmic concentration of 5-HT is increased above physiologically relevant levels by the inhibition of MAO A, MAO B becomes active. [ ¹⁴C] 5-HT uptake into synaptosomes was reduced by decreasing the V _max of [¹⁴C] 5-HT uptake. One mechanism for a decrease in the V_max could be the increase in the cytoplasmic concentration of 5-HT.

Key Words: monoamine oxidase • serotonin • serotonin uptake • serotonin metabolism • monoamine oxidase inhibition

Journal of Psychopharmacology, Vol. 7, No. 2, 181-189 (1993)
DOI: 10.1177/026988119300700206


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