Increased Cerebrospinal Fluid Dopamine and 3,4-Dihydroxyphenylacetic Acid Levels in Huntington''s Disease: Evidence for an Overactive Dopaminergic Brain Transmission

Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) in the CSF of patients with Huntington's disease (HD) were measured by HPLC. CSF DA, DOPAC, and MHPG levels were found to be increased in HD patients. Levels of HVA, 5-HIAA, and NA in the CSF of HD patients did not differ from those of controls. Changes in CSF DA and DOPAC levels were consistent with previous findings of increased DA tissue content in some brain areas of patients with HD. These results suggest that CSF DOPAC levels could be a more reliable index of overactive dopaminergic brain systems in HD than CSF HVA levels.     

Ventricular Cerebrospinal Fluid Monoamine Transmitter and Metabolite Concentrations Reflect Human Brain Neurochemistry in Autopsy Cases

Concentrations of dopamine (DA), its metabolites 3-methoxytyramine and homovanillic acid (HVA), noradrenaline (NA), its metabolites normetanephrine (NM) and 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT, serotonin), and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in 14 brain regions and in CSF from the third ventricle of 27 human autopsy cases. In addition, in six cases, lumbar CSF was obtained. Monoamine concentrations were determined by reversed-phase liquid chromatography with electrochemical detection. Ventricular/lumbar CSF ratios indicated persistence of rostrocaudal gradients for HVA and 5-HIAA post mortem. Ventricular CSF concentrations of DA and HVA correlated positively with striatal DA and HVA. CSF NA correlated positively with NA in hypothalamus, and CSF MHPG with levels of MHPG in hypothalamus, temporal cortex, and pons, whereas CSF NM concentration showed positive correlations with NM in striatum, pons, cingulate cortex, and olfactory tubercle. CSF 5-HT concentrations correlated positively with 5-HT in caudate nucleus, whereas the concentration of CSF 5-HIAA correlated to 5-HIAA levels in thalamus, hypothalamus, and the cortical areas. These data suggest a specific topographic origin for monoamine neurotransmitters and their metabolites in human ventricular CSF and support the contention that CSF measurements are useful indices of central monoaminergic activity in man.     

Rat brain monoamine and serotonin S2 receptor changes during pregnancy

The concentrations of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites were determined in 5 brain areas of non-pregnant, 15 and 20 day pregnant and 4 day post-partum rats. Striatal 5-HT content was significantly lower in 15 and 20 day pregnant rats than in estrous controls. A significant decrease in striatal and frontal cortex 5-hydroxyindole-3-acetic acid (5-HIAA) concentration was observed in 15 day pregnant rats. Significant increases in hypothalamic and hippocampal NA levels were observed at 4 days post-partum. Frontal cortex serotonin S2 receptorKd was reduced in 4 day post-partum rats. There was no significant change in S2 receptorB _max during pregnancy. Levels of progesterone were negatively correlated with striatal DA, homovanillic acid (HVA), 5-HT, and 5-HIAA levels, hypothalamic DA, hippocampal 5-HT, and frontal cortex 5-HIAA values as well as striatal HVA to DA, and HVA to 3,4-dihydroxyphenylacetic acid (DOPAC) ratios and amygdaloid HVA to DOPAC ratios. The limbic neurotransmitter changes might possibly contribute to mood changes which occur during pregnancy and post-partum.     

Changes in rat brain monoamine turnover following chronic antidepressant administration

Changes in rat brain monoamine turnover were studied following the chronic administration of five agents which markedly differ in their patterns of monoamine uptake inhibition. Compounds (10 mg/kg, i.p.) were injected once daily for 14 days and experiments undertaken 24 h after the last injection. Chronic administration of desipramine or mianserin elevated brain MOPEG-SO₄ content and the α-MT-induced reduction in brain NA levels was enhanced by chronic desipramine. either antidepressant altered turnover of brain DA or 5-HT. Steady state levels of brain 5-HIAA or striatal levels of DOPAC or HVA were also unchanged. Chronically administered Org 6582, a selective inhibitor of 5-HT uptake, decreased basal and attenuated the probenecid-induced increase iin brain 5-HIAA levels. Chronic Org 6582 had no effect on NA or DA turnover and on the levels of MOPEG-SO₄, DOPAC or HVA. Neither maprotiline nor chlorimipramine altered turnover of NA, DA or 5-HT or levels of metabolites. Thus, in contrast to the acute situation, chronically administered desipramine increases rat brain NA turnover. Conversely, acute and chronic Org 6582 administration yield similar findings, viz. a decrease in turnover. These observations suggest that rat brain 5-HT systems are more resistant than NA systems to adaptive changes following a prolonged inhibition of monoamine uptake.     

Brain amines and neocortical EEG in young and aged rats

1. Frontal and parieto-occipital electroencephalography (EEG) of young (4 months-old) and aged (17 and 22 months-old) Wistar rats were analyzed, both during movement and during waking immobility. 2. The levels of monoamines, serotonin and their metabolites were measured from the frontal cortex, parieto-occipital cortex, hippocampus, brainstem and midbrain. 3. In aged rats, as compared to young rats, the most apparent changes of the quantitative EEG spectrum were the decreased amplitude of alpha (5-10 Hz) and beta (10-20 Hz) frequency bands in the frontal and parieto-occipital cortices during both movement and waking immobility behavior (p less than 0.05). 4. The levels of dopamine (DA), homovanillinic acid (HVA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) or the ratios of 5-HT/5-HIAA and DA/HVA did not differ between young and aged rats in any brain region studied, with the exceptions of brainstem DA and parieto-occipital 5-HIAA, which were elevated in aged rats (p less than 0.05). 5. In the frontal cortex, hippocampus and midbrain, noradrenaline (NA) levels of aged rats were slightly increased as compared to young rats (p less than 0.05). 6. NA levels of the parieto-occipital cortex and brainstem did not change during aging. 7. Furthermore, there were no clear correlations between the decreased amplitude of the quantitative EEG spectrum and monoamine or serotonin concentrations, or the ratios of 5-HT/5-HIAA and DA/HVA in the cerebral cortex of aging Wistar rat.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simultaneous determination of catecholamines in rat brain tissue by high-performance liquid chromatography

A novel and highly sensitive method has been developed for the determination of catecholamines [noradrenaline (NA), dopamine (DA), serotonin (5-HT) and their metabolites 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA)] in brain tissue. The method uses isocratic reversed-phase HPLC with amperometric end-point detection. The calibration curve was linear over the range 10–150 pg on-column. The assay limits of detection for NA, DA, 5-HT, 5-HIAA and HVA were 3.8, 3.8, 6.8, 5 and 7.5 pg on-column, respectively. The mean inter- and intra-assay relative standard deviations (RSDs) over the range of the standard curve were less than 5%. The absolute recoveries averaged 99.1%, 99.5%, 97.7%, 99.5% and 98.8% for NA, DA, 5-HT, 5-HIAA and HVA, respectively.     

Determination of Picomole Amounts of Dopamine, Noradrenaline, 3,4-Dihydroxyphenylalanine, 3,4-Dihydroxyphenylacetic Acid, Homovanillic Acid, and 5-Hydroxyindolacetic Acid in Nervous Tissue After One-Step Purification on Sephadex G-10, Using High-Performance Liquid Chromatography with a Novel Type of Electrochemical Detection

A determination of dopamine (DA), noradrenaline (NA), 3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindolacetic acid (5-HIAA) in nervous tissue is described. The method is based on a rapidly performed isolation of DA, NA, DOPA, DOPAC, HVA, and 5-HIAA from one single nervous tissue sample on small columns of Sephadex G-10, followed by reverse-phase high-performance liquid chromatography with electrochemical detection. A new type of electrochemical detector based on a rotating disk electrode (RDE) was used. The rotating disc electrode was found to be a reliable and sensitive amperometric detector with several advantages over the currently used thin-layer cells. The detector appeared very useful for routine analysis. Practical details are given for the routine use of the RDE. Brain samples containing no more than 75-150 pg (DA, DOPA, DOPAC, HVA, and 5-HIAA) or 500 pg (NA) could be reproducibly assayed with high recovery (approx. 85%) and precision (approx. 5%), without the use of internal standards. Endogenous concentrations of DA, NA, DOPA, DOPAC, HVA, and 5-HIAA were determined in eight brain structures.     

Correlations between aminergic metabolites simultaneously obtained from human CSF and brain

Brain and cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were simultaneously measured in 48 individuals at autopsy. Concentrations of 5-HIAA and HVA in the cerebral cortex were positively correlated with their levels in the CSF for the same individual. Additionally a positive correlation was observed between postmortem CSF levels of 5-HIAA and HVA and a significant concentration gradient for both metabolites was observed in serial fractions of CSF. These findings suggest that determinations of 5-HIAA and HVA in CSF from living individuals may reflect brain metabolite levels as well as the functional activity of these specific neuronal systems.     

Enhancement of Brain Dopamine Metabolism by Tyrosine During Immobilisation: An In Vivo Study Using Repeated Cerebrospinal Fluid Sampling in Conscious Rats

Central dopamine (DA) and 5-hydroxytryptamine (5-HT) metabolism was monitored in conscious, freely moving rats by determination of levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) in CSF samples withdrawn repeatedly from the cisterna magna and treated with acid to hydrolyse DOPAC and HVA conjugates. The effect of tyrosine on DA metabolism was investigated. Time courses of metabolite concentrations in individual rats in a quiet room showed that tyrosine (20, 50, or 200 mg/kg i.p.) was without significant effect; brain changes were essentially in agreement. However, the increases of CSF DOPAC and HVA levels that occurred on immobilisation for 2 h were further enhanced by tyrosine (200 mg/kg). The associated increases of 5-HIAA level were unaffected. The corresponding increases of DA metabolite concentrations in the brains of immobilised rats given tyrosine were less marked than the CSF changes and only reached significance for "rest of brain" DOPAC. The CSF studies revealed large interindividual variation in the magnitude and duration of the effects of immobilisation on transmitter amine metabolism. These results may help toward the elucidation of possible relationships between the neurochemical and behavioural effects of stress.     

Comparative analysis of indices of central dopaminergic functions in man

Various postulated indices of central dopaminergic activity - cerebrospinal fluid (CSF) dopamine (DA), dihydroxy-phenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), plasma NA, serum prolactin, serum dopamine-β-hydroxylase (DBH), and platelet monoamine oxidase (MAO) activity - were measured in 30 drug-free inpatients. The mean values and the ranges were similar to those described in the literature. Plasma NA showed significant positive correlation with age. Significant positive correlation was found between CSF DA and its metabolites DOPAC and HVA. Serum DBH activity showed a slight but significant inverse correlation with CSF DA and its two metabolites. CSF NA showed a significant positive correlation with CSF DOPAC, but only in females. Serum DBH activity had no significant correlation either with CSF or with plasma NA levels. These findings suggest that either CSF HVA or DOPAC and DA may be useful indicators of DA metabolism in humans. Serum DBH activity may be in relationship with the central dopaminergic functions.     

Prenatal Exposure to Ozone Disrupts Cerebellar Monoamine Contents in Newborn Rats

Ozone (O3) is widely distributed in environments with high levels of air pollution. Since cerebellar morphologic disruptions have been reported with prenatal O3 exposure, O3 may have an effect on some neurotransmitter systems, such as monoamines. In order to test this hypothesis, we used 60 male rats taken from either, mothers exposed to 1 ppm of O3 during the entire pregnancy, or from mothers breathing filtered and clean air during pregnancy. The cerebellum was extracted at 0, 5, and 10 postnatal days. Tissues were processed in order to analyze by HPLC, dopamine (DA) levels, 3,4 dihydroxyphenilacetic acid (DOPAC) and homovanillic acid (HVA), norepinephrine (NA), serotonin, and 5-hydroxy-indole-acetic acid (5-HIAA) contents. Results showed a decrease of DA, NA, DOPAC and HVA mainly in 0 and 5 postnatal days. There were no changes in 5-HT levels, and 5-HIAA showed an increase after 10 postnatal days. DOPAC + HVA/DA ratio showed changes in 0 and 10 postnatal days, while 5-HIAA/5-HT ratio showed a slight decrease in 0 days. The data suggest that prenatal O3 exposure disrupts the cerebellar catecholamine system rather than the indole-amine system. Disruptions in cerebellar NA could lead to ataxic symptoms and also could limit recovery after cortical brain damage in adults. These finding are important given that recovery mechanisms observed in animals are also observed in humans.     

Monoamine Neurotransmitter Metabolites in the Cerebrospinal Fluid of a Group of Hybrid Baboons (Papio hamadryas × P. anubis)

Comparatively little is known about the pathways of proximate causation that link divergent genotypes, via neurophysiological differences, to distinct, species-specific social behaviors and systems. One approach to the problem compares gross activity levels of monoamine neurotransmitters (norepinephrine, dopamine, and serotonin), evidenced by their metabolites —3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), respectively— in cerebrospinal fluid (CSF). We have applied this method to Papio hamadryas and P. anubis, closely related baboon species with divergent social behavior, living in the Awash National Park (ANP), Ethiopia. We had previously shown that adult males of the two species differ in the ratio of HVA to 5-HIAA, and in concentrations of MHPG and HVA, but not 5-HIAA. Here, we compare monoamine metabolite levels of the parental species with those of 49 members of a naturally formed, multigenerational hamadryas × anubis hybrid group. We cage-trapped the baboons in July 1998, sampled their CSF by cisternal puncture, and assayed monoamine metabolites by high-performance liquid chromatography. Previous findings suggested, anomalously, that hybrid males showed the high 5-HIAA levels predicted by the low-serotonin–early-dispersal hypothesis (originally based on observation of rhesus macaques, Macaca mulatta), while hamadryas did not. The present study failed to find higher 5-HIAA levels in hybrids, resolving the anomaly, but leaving the previous result unexplained. Among adult females (underrepresented in our sample) and juveniles, metabolite levels of the hybrids did not differ significantly from either parental species. Overall, adult male hybrids resembled anubis in HVA and HVA/5-HIAA ratio, but did not show the low MHPG levels characteristic of that species. Consistent with a significant genetic influence on species differences in these metabolites, the adult hybrids showed intermediate means and greater intra-population diversity than the parental species for most variables, but showed no indication of hybrid dysgenesis in the form of low intermetabolite correlation. To the contrary, an enhanced HVA–MHPG correlation in the hybrids suggested a species-associated factor (not necessarily genetic) influencing both of these monoamine neurotransmitter systems.     

In vivo release of endogenous dopamine, 5-hydroxytryptamine and some of their metabolites from rat caudate nucleus by phenylethylamine

The in vivo release of endogenous 3,4-dihydroxyphenylethylamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT), and of 5-hydroxytryptamine (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), has been measured in the caudate nucleus of the anesthetized rat. A push-pull cannula was implanted into the brain, and the tissue perfused with artificial CSF or artificial CSF containing 5×10^–4 M phenylethylamine. The perfusate was collected and analyzed for DA, 5-HT and their metabolites by high performance liquid chromatography with electrochemical detection (HPLC-ECD). DA was released by phenylethylamine at rates significantly greater than its basal rate. 3-MT and 5-HT were undetectable in perfusates collected under basal conditions, but could be detected readlly during phenylethylamine stimulation. DOPAC, HVA and 5-HIAA concentrations were not significantly affected by phenylethylamine. The results suggest (1) that phenylethylamine may exert its behavioural effects through increased release of both DA and 5-HT, and (2) that in vivo measurements of the acid metabolites alone may not be indicative of the release of the amines.Special Issue Dedicated to Dr. Abel Lajtha.     

Kinetics of Drug-Induced Changes in Dopamine and Serotonin Metabolite Concentrations in the CSF of the Rat

Cerebrospinal fluid (CSF) was removed at a constant flow rate of 1 microliter/min from the third ventricle of anesthetized rats. Every 15 min, CSF dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined by direct injection of CSF into a liquid chromatographic system coupled with electrochemical detection. Mean CSF concentrations of DOPAC, HVA, and 5-HIAA were 1.29 microM, 0.88 microM, and 2.00 microM, respectively. In order to determine the turnover rates of dopamine (DA) and serotonin, experiments using monoamine oxidase (MAO) inhibition were performed. Tranylcypromine (20 mg/kg i.p.) induced a sharp exponential decrease of CSF DOPAC, HVA, and 5-HIAA, with respective half-lives of 15.60 min, 16.91 min, and 77.23 min. Their respective turnover rates were 3.74, 2.22, and 1.18 nmol X ml-1 X h-1. m-Hydroxybenzylhydrazine (NSD-1015, 100 mg/kg i.p.) and monofluoromethyl-DOPA (100 mg/kg i.p.), two decarboxylase inhibitors, induced a slow exponential decrease of all three CSF metabolites. alpha-Methyl-p-tyrosine (250 mg/kg i.p.) also induced a slow exponential decrease of DOPAC and HVA. These decreases of CSF DOPAC and HVA induced by DA synthesis inhibitors may reflect the turnover of DA in vivo. Haloperidol (0.5 mg/kg i.p.) considerably enhanced CSF DOPAC and HVA without affecting 5-HIAA, confirming that dopaminergic receptors modulate DA neurotransmission in vivo. Haloperidol administered 1.5 h after NSD-1015 did not increase DOPAC and HVA, in contrast to reserpine (5 mg/kg i.p.) injected under the same conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Significant correlation between cerebrospinal fluid and brain levels of norepinephrine, serotonin and acetylcholine in anesthetized rats

The present study was undertaken to determine cerebrospinal fluid (CSF) and brain levels of norepinephrine (NE), serotonin (5-HT) and their metabolites--3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylacetic acid (HVA) and 5-hydroxyindole-3-acetic acid (5-HIAA)--in rats pretreated with 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT). In the 6-OHDA pretreated rats, both CSF and brain concentrations of NE, DOPAC and HVA sustained significant decreases as compared with those in non-treated rats. Positive and significant correlations between CSF and brain levels were observed in respect to NE, DOPAC and HVA. In 5,7-DHT pretreated rats, both CSF and brain concentrations of 5-HT and 5-HIAA were significantly decreased. A positive and significant correlation between CSF and brain levels in respect to 5-HT and 5-HIAA was observed. Further studies were carried out to determine ACh levels of both the CSF and the brain in microspheres (MS)-treated rats, which are used as a model of microembolization. The CSF ACh concentrations in MS-treated groups were significantly decreased as compared with those in non-treated rats. The brain ACh contents also tended to decrease in this group. A positive and significant correlation was observed between CSF and brain levels of ACh. These findings suggest that NE, 5-HT and ACh concentrations in the CSF are direct indications of central noradrenergic, serotonergic and cholinergic nerve activity, respectively.     

Determination of tyrosine, tryptophan and their metabolic derivatives by liquid chromatography-electrochemical detection: application to post mortem samples from patients with Parkinson's and Alzheimer's disease

A procedure is described for the rapid determination of the major indoles and catechols. Analysis with picogram detection limits was done by high-pressure liquid chromatography on a C18 reverse-phase column using electrochemical detection (LCEC). This method provides a comprehensive list of compounds which can be simultaneously determined in brain samples and for which there is no necessity of derivatization or pre-column purification. The regional distribution of 9 neurochemicals from rat brain and the levels of 10 neurochemicals from human brain are presented. DOPA, TYR, NE, MHPG, DOPAC, 5-HIAA, TRP, DA, HVA, 3-MT and 5-HT were detected in the caudate nucleus and putamen. The levels of neurochemicals from the caudate and putamen of a demented patient with Parkinson's disease were variably decreased; catechol and indole losses were greatest in the putamen. The levels of neurochemicals in the caudate and putamen of patients with Alzheimer's disease (SDAT) were also variably decreased; loss of NE was seen only in putamen and losses of DA, HVA and 5-HT were uniform across both caudate and putamen. The CSF of SDAT patients showed changes in NE only.     

Simultaneous quantification of homovanillic acid and 5-hydroxyindoleacetic acid in cerebrospinal fluid by mass fragmentography

A mass fragmentographic technique for the simultaneous quantification of HVA and 5-HIAA in CSF was described. Deuterium labelled analogues of the acids were used as internal standards. Derivatives of the compounds were prepared by reacting CSF extracts with a mixture of pentafluoropropanol and pentafluoropropionic anhydride. Fragments set into focus were the molecular ion of the HVA derivatives and M⁺ ?177 of the 5-HIAA derivatives. The experimental error was below 7% for both acids and the recovery of authentic compounds added to CSF was 93–96%. With an AVA allowing simultaneous recording of four mass numbers, both acids could be determined concomitantly. The technique would be appropriate for analysis of large numbers of samples especially when it is of interest to determine the relation between levels of HVA and 5-HIAA in CSF.     

INHIBITION BY APOMORPHINE OF DOPAMINE DEAMINATION IN THE RAT BRAIN

Abstract— Apomorphine (A) inhibited dopamine deamination by rat brain mitochondria, but did not influence catechol- O -methyltransferase (COMT) activity by brain homogenates. The administration of apomorphine (10mg/kg i.p.) to normal rats increased brain dopamine (DA) by 34 per cent and decreased homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) by 60 per cent. In rats treated with reserpine 15 min prior to A, the latter prevented the rise of cerebral HVA and DOPAC and the depletion of DA produced by the former. Finally, A decreased the L-DOPA-induced accumulation of HVA and DOPAC in the rat basal ganglia. These results indicate that A inhibits DA deamination by monoamine oxidase.
This inhibition seems to be specific since apomorphine did not influence 5-HIAA levels in normal rats and prevented neither central 5-HT depletion nor 5-HIAA rise induced by reserpine.     

SEROTONIN AND DOPAMINE METABOLITES IN BRAIN REGIONS AND CEREBROSPINAL FLUID OF A PRIMATE SPECIES: EFFECTS OF KETAMINE AND FLUPHENAZINE

Abstract— The concentration of dopamine (DA) and serotonin (5-HT) metabolites in brain regions was not altered by doses of ketamine (10mg/kg) which induced dissociative anesthesia in a primate species. Cercopithecus aethiops. Fluphenazine (1.0mg/kg) increased homovanillic acid (HVA) content in all brain regions examined. An increase in HVA and 5-hydroxyindoleacetic acid (5-HIAA) concentration was observed in cisternal CSF 4 h after ketamine without a concomitant change in the brain concentration of these metabolites.     

Motor Activity Increases Tryptophan, 5-Hydroxyindoleacetic Acid, and Homovanillic Acid in Ventricular Cerebrospinal Fluid of the Conscious Rat

An investigation was made into the effects of running (1 h at 20 m/min) on central serotonergic and dopaminergic metabolism in trained rats. Methodology involved continuous withdrawal of cerebrospinal fluid (CSF) from the third ventricle of conscious rats and measurements of tryptophan (TRP), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels during a 2 h post-exercise period. All three compounds were increased during the hour following exercise and returned to their basal values within an hour later. CSF flow rate was stable when metabolite levels were elevated. Brain determinations indicated that CSF metabolite variations only qualitatively paralleled brain changes. Indeed, post-exercise TRP, 5-HIAA, and HVA levels were increased to a greater extent in brain when compared to CSF. It is suggested that increased serotonergic and dopaminergic metabolism, caused by motor activity, may be involved in the behavioral effects of exercise.