Does in vivo voltammetry in the hippocampus measure 5-HT release?
In vivo voltammetry enables catecholamine and 5-hydroxytryptamine (5-HT) release to be directly determined in the brains of conscious unrestrained animals. This study concerned the validation of the measurement of 5-HT release using scanning voltammetry at chronically implanted carbon paste/epoxy resin glass microelectrodes in the rat hippocampus. Automated recordings of the current produced by applying a ramp (100 mV/s) potential (0-1 V) to the electrode at 5 min intervals were made over a period of several hours. A current peak at 0.35-0.4 V corresponded to that produced by solutions of 5-HT in vitro. The effect of a number of drug known to affect 5-HT synthesis and release was then studied in vivo. p-Chloroamphetamine (PCA) caused an increase in the peak which correlated with a '5-HT behavioural syndrome'. p-Chlorophenylalanine caused a reduction in the peak and prevented both the increase seen with PCA and the PCA induced behavior. Fluoxetine and L-tryptophan also led to increases in signal; all these results were consistent with the signal reflecting extraneuronal 5-HT. However 5-hydroxyindoleacetic acid (5HIAA) also oxidizes at 0.35-0.4 V in vitro. Probenecid, which blocks 5HIAA egress from the brain caused a large increase in the hippocampal signal. The monoamine oxidase inhibitors pargyline and nialamide, which increases 5-HT and reduce 5HIAA levels, had no significant effect on the signal. These results, together with the greater increase in signal following probenecid than tryptophan and the delayed increase after tryptophan, and interpreted as implying that extraneuronal 5HIAA and 5-HT contribute approximately equally to the hippocampal signal. We conclude that this method gives information distinct from and complementary to biochemical estimations, and offers great scope for the investigation of the role of 5-hydroxyindole release in drug and environmental effects on behaviour.
D000818:Animals; D004594:Electrophysiology; D010134:Fenclonine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D010293:Pargyline / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000494:pharmacology
D005473:Fluoxetine; D012701:Serotonin; D014364:Tryptophan; D010293:Pargyline; D011339:Probenecid; D010134:Fenclonine