Negative feedback control of serotonin release in vivo: comparison of 5-hydroxyindolacetic acid levels measured by voltammetry in conscious rats and by biochemical techniques.

All evidence that serotonin release from central neurones is controlled by a negative feedback mechanism comes from in vitro studies. To study this problem in vivo we performed differential pulse voltammetry in conscious rats, in which carbon fibre electrodes had been implanted 2-15 weeks previously. The effects of monoamine oxidase inhibition (which decreases the amount of 5-hydroxyindoleacetic acid), as well as that of probenecid (which increases 5-hydroxyindoleacetic acid), suggests that 5-hydroxyindoleacetic acid rather than serotonin is measured. Blockade of the presynaptic serotoninergic autoreceptors by methiothepin, metergoline or quipazine led to an increase in differential current of the peak attributed to 5-hydroxyindoleacetic acid in hippocampus, hypothalamus and striatum. Stimulation of these receptors by m-chlorophenylpiperazine, MK-212 or LSD decreased the signal attributed to 5-hydroxyindoleacetic acid. A decrease in the signal was also seen with cinanserin. Stimulation of presynaptic alpha 2-adrenoreceptors by clonidine decreased the signal. Metergoline, quipazine and cinanserin showed biphasic effects, and no effect was observed with methysergide. In general, a reasonable agreement with the results of Baumann & Waldmeier obtained in vitro with electrically stimulated [3H]serotonin prelabelled cortex slices was achieved with differential pulse voltammetry. Only partial agreement with the results of voltammetry was obtained if 5-hydroxyindoleacetic acid was determined biochemically under comparable conditions. Qualitatively, the effects observed with methiothepin, m-chlorophenylpiperazine, clonidine and LSD were in good agreement with those measured with voltammetry as well as with the in vitro effects obtained in electrically stimulated cortex slices. No, or only partial correlation with the results obtained with voltammetry was found with MK 212, cinanserin, metergoline and quipazine. It is concluded that voltammetry preferentially measures extraneuronal 5-hydroxyindoleacetic acid rather than overall changes of this metabolite.