3,4‐Dihydroxyphenylethylamine and 5‐Hydroxytryptamine Metabolism in the Rat: Acidic Metabolites in Cisternal Cerebrospinal Fluid Before and After Giving Probenecid

Abstract

3,4-Dihydroxyphenylethylamine (DA, dopamine) and 5-hydroxytryptamine (5-HT) turnover values were determined in freely moving male rats by measuring the rates of accumulation of the acidic metabolites of the above transmitters, i.e., 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in cisternal cerebrospinal fluid (CSF) samples after probenecid (200 mg/kg i.p.) administration. Determinations on samples before and after acid hydrolysis showed that the latter procedure was necessary for DA turnover determination. Thus whereas total (DOPAC + HVA) increased linearly with time after probenecid, free (DOPAC + HVA) did not. This was because the percentage of DOPAC + HVA in conjugated form increased with time. Determinations on a group of 28 rats during the dark (red light) period showed that cisternal amine metabolite concentrations before probenecid injection did not parallel turnover values. This was probably because individual differences in metabolite egress strongly affect the pre-probenecid values. The poor correlations between CSF tryptophan and 5-HT turnover suggested that differences of brain tryptophan concentration were not major determinants of differences of brain 5-HT metabolism within this group of normal rats. Considering that the rats were of similar weight and that the turnover values were all determined at approximately the same time of day, the three- to fourfold ranges of the turnover values are remarkable. The positive correlation between the DA and 5-HT turnovers of individual rats suggests the existence of common effects on DA and 5-HT turnover in normal rats.

Stability, clearance, and disposition of intraventricularly administered oligodeoxynucleotides: implications for therapeutic application within the central nervous system.

“…The endothelium of small vessels also appears highly fluorescent, suggesting uptake of material that has been cleared into the vasculature. After continuous infusion of phosphorothioate ODN for 1 week (1.5 nmol/hr), a gradient distribution of ODN is less apparent, but marked 10 uptake of fluorescent material is now observed in many cell bodies scattered throughout the tissue section (Fig. SB).…”

Development of a Percutaneous Cerebrospinal Fluid Collection Technique in F-344 Rats and Evaluation of Cell Counts and Total Protein Concentrations

“…However, with the advent of more sensitive assay techniques such as enzyme-linked immunosorbent assay and high-performance liquid chromatography (Klockowski and Levy, 1987), the low CSF yield from rats is no longer a limitation in utilization for biomarker measurement in a variety of toxicities and neurological disorders. Numerous techniques have been described for CSF collection in rats permanently implanted with cannulae or by guided cannulae (Curzon et al, 1985;De La Riva and Yeo, 1985;Jolkkonen et al, 1986;Sanvitto et al, 1987;Dingemanse et al, 1988;Sokomba et al, 1988;Takemoto, 1991;Westergren and Johansson, 1991;Halonen et al, 1992;Consiglio and Lucion, 2000). Ylitalo et al (1976) and Klockowski and Levy (1987) described the collection of CSF from the cisterna magna of anesthetized rats via percutaneous puncture.…”

“…Ylitalo et al (1976) and Klockowski and Levy (1987) described the collection of CSF from the cisterna magna of anesthetized rats via percutaneous puncture. CSF from rats is routinely analyzed in many pharmaco-toxicologic (Curzon et al, 1985;De La Riva and Yeo, 1985;Jolkkonen et al, 1986;Kornhuber et al, 1986b;Takemoto, 1991) and biochemistry (Ylitalo et al, 1976;Westergren and Johansson, 1991) research studies. Although, there are infrequent reports of the normal cellular and protein composition of CSF of several strains of laboratory rats (Luxton et al, 1989), the present literature lacks any such reports about Fischer-344 rats.…”

Monoamine Metabolite Levels in Rat CSF: Kinetic Studies

“…DOPAC, HVA and 5-HIAA) from CSF with probenecid, and measured the rate of their accumulation, shown to be 5-HIAA proportional to the turnover of the parent amines (Elghozi ei al. 1983b;Sarna et al 1983;Hutson et al 1984;Curzon et al 1985). However, it has become evident that there is a large (up to 3or 4-fold) variation between individual rats in the turnover values obtained using this methodology (Elghozi et al 1983b;Curzon et al 1985).…”

“…1983b;Sarna et al 1983;Hutson et al 1984;Curzon et al 1985). For example, investigators have blocked the egress of the acidic metabolites (e.g.…”