Measurement of 5-hydroxytryptamine synthesis and metabolism in selected discrete regions of the rat brain using high performance liquid chromatography and electrochemical detection: pharmacological manipulations.
High performance liquid chromatography coupled with electrochemical detection (LCEC) was employed to measure 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptophan (5-HTP) in the suprachiasmatic (SCN), medial preoptic (MPO) and arcuate (AN) nuclei as well as the median eminence (ME) and striatum (ST) of individual rat brains. Biochemical estimations of changes in 5-HT neuronal activity were made by measuring: (1) concentrations of 5-HT and 5-HIAA and (2) the rate of 5-HT synthesis (5-HTP accumulation following the administration of NSD 1015, an inhibitor of aromatic L-amino acid decarboxylase) after the administration of pharmacological agents known to influence these neurons. Pargyline increased the concentration of 5-HT and decreased the concentration of 5-HIAA while probenecid increased the concentration of 5-HIAA in all 5 brain regions. At both 2 and 24 hours after reserpine the concentration of 5-HT decreased, 5-HIAA increased or did not change, and the rate of 5-HT synthesis increased. In most of the brain regions blockers of 5-HT neuronal uptake (fluoxetine, chlorimipramine) did not influence 5-HT or 5-HIAA concentrations dramatically, but increased the rate of 5-HT synthesis. L-tryptophan generally increased the concentrations of 5-HT and 5-HIAA as well as the rate of accumulation of 5-HTP in all regions except the ME where 5-HIAA and 5-HTP concentrations both were unaffected. These results reveal that the method using LCEC is sensitive enough to detect pharmacologically-induced changes in 5-HT metabolism and synthesis in discrete regions of rat brain. The drugs examined in the present study generally caused similar changes in 5-HT dynamics in all 5 brain regions examined.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D010293:Pargyline / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000096:biosynthesis*; D014364:Tryptophan / Q000494:pharmacology
D006834:Hydrazines; D012701:Serotonin; D012110:Reserpine; D014364:Tryptophan; D010293:Pargyline; C004297:3-hydroxybenzylhydrazine; D011339:Probenecid