Measurement of serotonin turnover rate in rat dorsal raphe nucleus by in vivo electrochemistry.
5-Hydroxytryptamine (5-HT; serotonin) turnover rate in dorsal raphe nucleus of the urethane-anesthetized rat was estimated by using the in vivo electrochemical detector to measure the decay of extraneuronal 5-hydroxyindole acetic acid (5-HIAA) after monoamine oxidase inhibition. Carbon paste electrodes were scanned by semiderivative voltammetry and revealed two peaks: one at +0.15 V and the other at +0.25 V. The higher potential peak is composed primarily of the 5-HT metabolite 5-HIAA. After administration of pargyline, 75 mg/kg i.p., this peak declined exponentially. Regression analysis of these data by an exponential decay model yielded the fractional rate constant 0.82 +/- 0.06 h-1 (mean +/- SEM). This rate constant of 5-HIAA disappearance measured by in vivo electrochemistry is identical to the rate constant found by others measuring 5-HIAA disappearance by direct tissue assay methods. In animals not treated with pargyline, tissue 5-HIAA concentrations in the dorsal raphe nucleus were measured by HPLC with electrochemical detection. The average 5-HT turnover rate calculated as the product of the fractional rate constant and steady-state tissue 5-HIAA concentration was 12.6 nmol/g/h. These results demonstrate that electrochemical detection of extraneuronal 5-HIAA combined with monoamine oxidase inhibition can be used to measure neurotransmitter turnover in vivo in a discrete brain region.
D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D004563:Electrochemistry; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010293:Pargyline / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D010293:Pargyline