In vivo measurement of noradrenaline and 3,4-dihydroxyphenylethyleneglycol in the rat hypothalamus by microdialysis: effects of various drugs affecting noradrenaline metabolism.
The extracellular concentrations of noradrenaline (NA) and 3,4-dihydroxyphenylethyleneglycol (DOPEG), one of the major metabolites of brain NA, in the hypothalamus of urethane-anesthetized rats were monitored by in vivo microdialysis followed by a sensitive and simultaneous determination of the two substances using high-performance liquid chromatography with electrochemical detection. The effects of various drugs that affect central NA metabolism were also examined. Resting levels of NA and DOPEG were constant during 1 and 6 hr after the start of perfusion, the mean values being 3.8 +/- 0.4 pg/30 min for NA and 107.5 +/- 9.1 pg/30 min for DOPEG (mean +/- S.E.M. of 7 animals). Tetrodotoxin (1 microM), when added to the perfusion medium, reduced the output of NA below the detection limit (0.5 pg) and also decreased the DOPEG output by 60%. Clonidine (0.2 mg/kg i.p.) caused a marked reduction in both the NA and DOPEG outputs, whereas yohimbine (5 mg/kg i.p.) significantly increased both the NA and DOPEG outputs. Desipramine (2 and 5 mg/kg i.p.) produced a dose-dependent increase in the NA output, although it caused a gradual decline of the DOPEG output. The atypical antidepressant mianserin (2 and 5 mg/kg i.p.), which possesses both alpha-2 antagonist and weak NA uptake inhibitory actions, produced a less marked increase in the NA output with no or only a small decrease in the DOPEG output. Therefore, it is suggested that monitoring the extracellular concentrations of both NA and DOPEG enables the discrimination between the action of drugs inhibiting the NA uptake and that of drugs enhancing the NA release, and that this method is useful to obtain detailed information about central NA metabolism in vivo.
Itoh
Y
Y
Department of Pharmacology, Okayama University Medical School, Japan.
Oishi
R
R
Nishibori
M
M
Saeki
K
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D003956:Dialysis / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D005110:Extracellular Space / Q000378:metabolism; D007031:Hypothalamus / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D008803:Mianserin / Q000494:pharmacology; D008832:Microchemistry / Q000379:methods; D009638:Norepinephrine / Q000032:analysis* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D008803:Mianserin; D015016:Yohimbine; D013779:Tetrodotoxin; D008734:Methoxyhydroxyphenylglycol; D003000:Clonidine; D003891:Desipramine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine