Detection of the release of 5-hydroxyindole compounds in the hypothalamus and the n. raphe dorsalis throughout the sleep-waking cycle and during stressful situations in the rat: a polygraphic and voltammetric approach.
In the present work, voltammetric method combined with polygraphic recordings were used in animals under long-term chronic conditions; the extracellular concentrations of 5-hydroxyindole compounds (5-OHles) and in particular 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hypothalamus and in the nucleus Raphe Dorsalis (n.RD). The hypothesis that extracellular detection of 5-HIAA, in animals under physiological conditions, might reflect serotonin (5-HT) release is suggested by the following observations: serotoninergic neurons are reported to contain only monoamine oxidase type B (MAO-B);--an inhibitor of such an enzyme, MDL 72145 (1 mg/kg), fails to decrease the extracellular 5-HIAA peak 3 height:--MAO type A is contained in non-5-HT cells or neurons;--only the inhibitor of this last type of enzyme (Clorgyline 2.5 mg/kg) induces a complete disappearance of the voltammetric signal. The 5-HIAA measured in the extracellular space thus comes from the 5-HT released and metabolized outside the 5-HT neurons. Throughout the sleep-waking cycle, 5-OHles release occurs following two different modes: 1--during sleep, in the vicinity of the 5-HT cellular bodies in the n.RD; this release might come from dendrites and be responsible for the 5-HT neuronal inhibition occurring during sleep; 2--during waking, at the level of the axonal nerve endings impinging on the hypothalamus; this release might be related to the synthesis of "hypnogenic factors". Finally, we have observed that in the hypothalamus, 30 min. of immobilization-stress (IS) induces a larger increase of the voltammetric signal (+80%) than a painful stimulation of the same duration (+30%); the possible link between the 5-OHles release occurring in this area during an IS and the subsequent paradoxical sleep rebound is discussed.
Houdouin
F
F
Département de Médecine Expérimentale, INSERM U52-CNRS UA 1195, Université Cl. Bernard, Lyon, France.
Cespuglio
R
R
Gharib
A
A
Sarda
N
N
Jouvet
M
M
D000499:Allylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003010:Clorgyline / Q000494:pharmacology; D004594:Electrophysiology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism*; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D011903:Raphe Nuclei / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D012149:Restraint, Physical; D012701:Serotonin / Q000378:metabolism; D012890:Sleep / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*
D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D000499:Allylamine; D006897:Hydroxyindoleacetic Acid; C040051:2-(3,4-dimethoxyphenyl)-3-fluoroallylamine; D010293:Pargyline; D003010:Clorgyline