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.

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.

Central 5-hydroxytryptamine (5-HT) and dopamine (DA) turnovers were estimated simultaneously in conscious freely moving rats kept on a 12-h dark/12-h light cycle by sampling cisternal CSF of each animal before and after giving probenecid and determining the accumulation of the acidic metabolites of the two amines. The turnovers of both transmitters and the clearances of their acid metabolites from the brain were shown to be significantly greater during the dark (red light) period than during the white light period.

No abstract

Portacaval anastomosis (PCA) in the rat may be a useful experimental model for examining endocrine changes that occur during cirrhosis of the liver. A marked reduction in diet intake and body weight occurs in rats after establishing the shunt and studies were undertaken to determine the relationship of these effects to the testicular atrophy that also follows PCA. Control, sham-operated animals, experiencing a reduction in food intake similar to that of the animals with a PCA, showed reduced plasma levels of LH and testosterone but also exhibited a marked testicular response to LH. This was consistent with increased sensitivity of the hypothalamic-pituitary axis to the negative feedback of gonadal steroids in chronically underfed animals. Male rats with a PCA exhibited similarly reduced levels of LH and testosterone, but showed poor secretory responses of the pituitary gland to LH releasing hormone (LH-RH) and of the testis to LH. Testicular atrophy and cessation of spermatogenesis occurred in the animals with a PCA. These results suggested that the effects of PCA on the pituitary-gonadal axis cannot simply be explained as a consequence of the restricted intake of diet. This was confirmed by the responses to castration. In both fed and underfed sham-operated rats, castration resulted in a rapid and sustained increase in plasma LH and both groups showed a marked LH secretory response to LH-RH. In contrast, in animals with a PCA castration had little effect on plasma LH and the pituitary response to LH-RH was still poor. The effects of PCA cannot be simply explained by impeded metabolism of gonadal steroids causing increased negative feedback on the hypothalamic-pituitary axis.