Concurrent determination of brain dopamine and 5-hydroxytryptamine turnovers in individual freely moving rats using repeated sampling of cerebrospinal fluid.
5-Hydroxytryptamine (5-HT) turnover and dopamine (DA) turnover values were obtained in individual conscious rats by measuring the rates of accumulation of 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in cisternal CSF samples taken from each rat at 0, 30, and 60 min after probenecid (200 mg/kg i.p.) administration. In a separate experiment, 5-HT and DA turnover values were determined in CSF, striatum, and rest of brain of groups of rats killed 0, 30, or 60 min after probenecid. Whole brain turnover values were calculated from striatal and rest of brain values. Mean turnover values using CSF were comparable with both procedures. DA turnover values were greater when based on total (i.e., free + conjugated) DA metabolites than when based on free metabolites. After partial inhibition of monoamine synthesis with the decarboxylase inhibitor DL-alpha- monofluoromethyl -DOPA ( MFMD , 100 mg/kg p.o.) DA and 5-HT turnover values were comparably reduced in whole brain, rest of brain, and CSF but more markedly reduced in the striatum. Mean DA and 5-HT turnover values obtained using CSF were similar with probenecid doses over the range 150-250 mg/kg i.p. but were variable when repeatedly determined in the same rats after administration of 200 mg/kg probenecid. Results in general show that the CSF procedure may be used to determine concurrently both 5-HT and DA turnover (when estimated from the sum of total but not free metabolites) and that it provides a good index of whole brain turnover of these transmitters in the conscious individual rat.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000134:cerebrospinal fluid; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000134:cerebrospinal fluid*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008750:Methyldopa / Q000031:analogs & derivatives / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000134:cerebrospinal fluid*
D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa; D011339:Probenecid; D004298:Dopamine; D006719:Homovanillic Acid