In vivo measurement of extracellular 5-hydroxytryptamine in hippocampus of the anaesthetized rat using microdialysis: changes in relation to 5-hydroxytryptaminergic neuronal activity.
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.
Sharp
T
T
MRC Clinical Pharmacology Unit, University Department of Clinical Pharmacology, Oxford, England.
Bramwell
S R
SR
Clark
D
D
Grahame-Smith
D G
DG
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000758:Anesthesia; D000818:Animals; D003956:Dialysis / Q000379:methods; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007267:Injections; D008297:Male; D009474:Neurons / Q000502:physiology*; D010477:Perfusion; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D013764:Tetrahydronaphthalenes; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D013779:Tetrodotoxin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin