alpha 2-Adrenoceptor agonists decrease free 3-methoxy-4-hydroxyphenylglycol in rat cerebrospinal fluid.
The effects of alpha 2-adrenoceptor agonists on the concentrations of monoamine metabolites in cisternal cerebrospinal fluid (CSF) of freely moving rats were determined. Clonidine and two new imidazole derivatives, detomidine and medetomidine, and diazepam (as a control substance) were administered in sedative doses and the concentrations of unconjugated 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in CSF were monitored for 48 h. The alpha 2-agonists caused a dose-dependent, statistically significant decrease in the concentration of MHPG in CSF compared to the concentration in animals treated with saline or diazepam. Detomidine caused a statistically significant increase in the concentration of 5-HIAA compared to control treatments. The present results demonstrate the usefulness of monitoring drug-induced alterations in central nervous system (CNS) noradrenergic activity by measuring free MHPG in repeatedly collected cisternal CSF samples from freely moving rats. The alpha 2-agonists reduced the concentration of MHPG in CSF, indicating a decreased release, metabolism and turnover of noradrenaline in the CNS.
Scheinin
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Virtanen
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Scheinin
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002404:Catheterization; D002851:Chromatography, High Pressure Liquid; D002946:Cisterna Magna; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006018:Glycols / Q000134:cerebrospinal fluid*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D006018:Glycols; D008734:Methoxyhydroxyphenylglycol