In vivo measurement of extracellular 5-hydroxytryptamine in hippocampus of the anaesthetized rat using microdialysis: changes in relation to 5-hydroxytryptaminergic neuronal activity

J Neurochem. 1989 Jul;53(1):234-40. doi: 10.1111/j.1471-4159.1989.tb07319.x.


The effect of manipulating the activity of central 5-hydroxytryptamine (5-HT) neurones on extracellular 5-HT in ventral hippocampus of the chloral hydrate-anaesthetized rat was studied using the brain perfusion method, microdialysis. Basal levels of 5-HT in the dialysates were close to the detection limits of our assay using HPLC with electrochemical detection. However, addition of the selective 5-HT reuptake inhibitor citalopram (10(-6) M) to the perfusion medium produced readily measurable amounts of dialysate 5-HT. Citalopram, therefore, was used throughout our experiments. Hippocampal dialysate levels of 5-HT sharply declined over the first hour after dialysis probe implantation, but then became constant. This stable output of 5-HT was reduced by 57% in rats treated 14 days previously with intracerebroventricular injections of the 5-HT neurotoxin 5,7-dihydroxytryptamine. Electrical stimulation (1-ms pulse width, 300 microA, 2-20 Hz) of the dorsal raphe nucleus for 20 min caused a rapid rise in hippocampal 5-HT output, which immediately declined on cessation of the stimulus and was frequency-dependent. Addition of tetrodotoxin (10(-6) M) to the perfusion medium reduced 5-HT levels to 75% of predrug values. Injection of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (0.5 and 2.5 micrograms) into the dorsal raphe nucleus caused a dose-related fall in hippocampal output of 5-HT compared to saline-injected controls. We conclude from these data that the spontaneous output of endogenous 5-HT into hippocampal dialysates, measured under our experimental conditions, predominantly originates from central 5-HT neurones and changes in accordance with their electrical activity.

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Anesthesia
  • Animals
  • Dialysis / methods
  • Electric Stimulation
  • Extracellular Space / metabolism*
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hydroxyindoleacetic Acid / metabolism
  • Injections
  • Male
  • Neurons / physiology*
  • Perfusion
  • Raphe Nuclei / physiology
  • Rats
  • Serotonin / metabolism*
  • Serotonin / physiology
  • Tetrahydronaphthalenes / pharmacology
  • Tetrodotoxin / pharmacology


  • Tetrahydronaphthalenes
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • Tetrodotoxin
  • Hydroxyindoleacetic Acid
  • 8-Hydroxy-2-(di-n-propylamino)tetralin