Neurotransmitter Changes in Guinea-Pig Brain Regions Following Soman Intoxication

The effects of the organophosphate acetylcholinesterase (AChE) inhibitor soman (31.2 micrograms/kg s.c.) on guinea-pig brain AChE, transmitter, and metabolite levels were investigated. Concentrations of acetylcholine (ACh) and choline (Ch), noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites, and six putative amino acid transmitters were determined concurrently in six brain regions. The brain AChE activity was maximally inhibited by 90%. The ACh content was elevated in most brain areas by 15 min, remaining at this level throughout the study. This increase reached statistical significance in the cortex, hippocampus, and striatum. The Ch level was significantly elevated in most areas by 60-120 min. In all regions, levels of NA were reduced, and levels of DA were maintained, but those of its metabolites increased. 5-HT levels were unchanged, but those of its metabolites showed a small increase. Changes in levels of amino acids were restricted to those areas where ACh levels were significantly raised: Aspartate levels fell, whereas gamma-aminobutyric acid levels rose. These findings are consistent with an initial increase in ACh content, resulting in secondary changes in DA and 5-HT turnover and release of NA and excitatory and inhibitory amino acid transmitters. This study can be used as a basis to investigate the effect of toxic agents and their treatments on the different transmitter systems.     

Distribution of catecholamines,serotonin, and their major metabolites in the rat cingulate,piriform-entorhinal,somatosensory, and visual cortex: A biochemical survey using high-performance liquid chromatography

The catecholamines noradrenline (NA), dopamine (DA), adrenaline (AD), the indoleamine 5-hydroxytryptamine (5-HT; serotonin), as well as some of their major metabolites were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, in four well-defined areas of the rat cerebral cortex: anterior cingulate (CIN;Cg1 and Cg3), piriform and entorhinal (PiEn), hind-limb primary somatosensory (SSC;HL) and primary visual (VIS; Oc1M and Oc1B). The concentrations of NA and that of its main metabolite 3-methoxy-4-hydroxyphenylglycol were highest in PiEn, had intermediate values in CIN and were lowest for SSC and VIS cortices. The DA levels were also highest in PiEn, intermediate in CIN, while the lowest values were in SSC and VIS cortices. The different DA/NA ratios support the hypothesis that they are indeed independent neurotransmitters. In addition, the levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid and 3-methoxytyramine paralleled the distribution of DA, thus confirming the presence of release sites, even in regions in which the low levels of this catecholamine could be interpreted simply as the precursor of NA. Traces of AD were detected in all the regions examined. The 5-HT contents, as well as that of its precursor 5-hydroxy-I-tryptophan and that of its metabolite 5-hydroxyindole-3-acetic acid were also found to be non-homogenous, with the highest levels measured in the PiEn and CIN regions.     

5-Hydroxy-3-Ethylamino-2-Oxindole Is Not Formed in Rat Brain Following a Neurotoxic Dose of Methamphetamine: Evidence that Methamphetamine Does Not Induce the Hydroxyl Radical-Mediated Oxidation of Serotonin

Abstract: Oxygen radicals have been implicated in the neurodegenerative and other neurobiological effects evoked by methamphetamine (MA) in the brain. It has been reported that shortly after a single large subcutaneous dose of MA to the rat, the serotonergic neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) is formed in the cortex and hippocampus. This somewhat controversial finding suggests that MA potentiates formation of the hydroxyl radical (HO^?) that oxidizes 5-hydroxytryptamine (5-HT) to 5,6-DHT, which, in turn, mediates the degeneration of serotonergic terminals. A major and more stable product of the in vitro HO^?-mediated oxidation of 5-HT is 5-hydroxy-3-ethylamino-2-oxindole (5-HEO). In this investigation, a method based on HPLC with electrochemical detection (HPLC-EC) has been developed that permits measurement of very low levels of 5-HEO in rat brain tissue in the presence of biogenic amine neurotransmitters/metabolites. After intracerebroventricular administration into rat brain, 5-HEO is transformed into a single major, but unknown, metabolite that can be detected by HPLC-EC. One hour after administration of MA (100 mg/kg s.c.) to the rat, massive decrements of 5-HT were observed in all regions of the brain examined (cortex, hippocampus, medulla and pons, midbrain, and striatum). However, 5-HEO, its unidentified metabolite, or 5,6-DHT were not detected as in vivo metabolites of 5-HT. MA administration, in particular to rats pretreated with pargyline, resulted in the formation of low levels of N-acetyl-5-hydroxytryptamine (NAc-5-HT) in all brain regions examined. These results suggest that MA does not potentiate the HO^?-mediated oxidation of 5-HT. Furthermore, the rapid MA-induced decrease of 5-HT might not only be related to oxidative deactivation of tryptophan hydroxylase, as demonstrated by other investigators, but also to the inhibition of tetrahydrobiopterin biosynthesis by NAc-5-HT. The massive decrements of 5-HT evoked by MA are accompanied by small or no corresponding increases in 5-hydroxyindole-3-acetic acid (5-HIAA) levels. This is due, in part, to the relatively rapid clearance of 5-HIAA from the brain and monoamine oxidase (MAO) inhibition by MA. However, the loss of 5-HT without corresponding increases in its metabolites point to other mechanisms that might deplete the neurotransmitter, such as oxidation by superoxide radical anion (O₂^??), a reaction that in vitro does not generate 5-HEO or 5,6-DHT but rather another putative neurotoxin, tryptamine-4,5-dione. One hour after administration, MA evokes large depletions of norepinephrine (NE) throughout the brain but somewhat smaller decrements of dopamine (DA) that are restricted to the nigrostriatal pathway. Furthermore, MA evokes a major shift in the metabolism of both NE and DA from the pathway mediated by MAO to that mediated by catechol-O-methyltransferase. The profound and widespread effects of MA on the noradrenergic system, but more anatomically localized influence on the dopaminergic system, suggests that NE in addition to DA, or unusual metabolites of these neurotransmitters, might play roles in the neurodegenerative effects evoked by this drug.     

Comparison of Serotonin and Dopamine Release in Substantia Nigra and Ventral Tegmental Area: Region and Species Differences

Abstract: In this study, we compare the electrically evoked, somatodendritic release of dopamine (DA) with axonal release of serotonin (5-HT) in the substantia nigra (SN) and ventral tegmental area (VTA) in vitro by using fast-scan cyclic voltammetry with carbon-fibre microelectrodes. Furthermore, we have examined transmitter release in these regions in guinea-pig compared with rat. Somatodendritic DA was released, as shown previously, in guinea-pig VTA, SN pars compacta (SNc), and occasionally in SN pars reticulata (SNr). 5-HT was rarely released, except in SNr, where nonetheless it only contributed to <30% of amine signals. In rat midbrain, somatodendritic DA release was evoked to a similar extent as in guinea-pig. However, a clear species difference was apparent; i.e., 5-HT and DA were detected equally in rat SNc, whereas in rat SNr, 5-HT was the predominant transmitter detected. Nevertheless, electrically evoked extracellular concentrations of 5-HT in SNc and SNr were, respectively, seven- and fourfold less than DA in SNc. 5-HT release was low in all regions in neonatal rat slices before the maturation of 5-HT terminals. Hence, axonal 5-HT transmission in midbrain exhibits both species and site selectivity. Moreover, whereas somatodendritic DA release is conventionally regarded as modest compared with axon terminal release in striatum, somatodendritic DA release can result in significantly greater extracellular levels than a transmitter released from axon terminals in the same locality.     

Microiontophoresis of biogenic amines on cortical neurons: amounts of NA, DA and 5-HT ejected, compared with tissue content

The present series of studies were carried out to quantify the amounts of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) ejected from iontophoresis micropipettes and that produce inhibitory and modulatory effects on cortical neurons, in the frontoparietal cortex of the rat and in the occipital cortex of the cat. Using radioactive isotopes of the biogenic amines the effective transport number (n) was found to be 0.08 for DA; 0.13 for NA, and 0.22 for 5-HT. In addition, similar determinations were made, for comparison purposes, of the transport numbers of the neurotransmitters acetylcholine (ACh; n = 0.44), gamma-amino-n-butyrate (GABA, n = 13), and glutamate (GLU; n = 0.27). The quantities ejected under in vivo conditions were then estimated using Faraday's formula and fell in the pmol range (10(-12) mol). The effects of DA, NA and 5-HT on cortical units were studied; the amounts ejected were compared with the endogenous tissue content of these amines, determined by means of specific and sensitive radioenzymatic assays in the regions where the microiontophoretic experiments were performed. These results are discussed in the light of the anatomical, biochemical and electrophysiological data suggesting a modulatory role for the biogenic amines in the cerebral neocortex.     

Regional distribution of dopamine, 5-hydroxytryptamine,and noradrenaline in the rat vas deferens

The concentrations of dopamine (DA), 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in the rat vas deferens divided in eight or four sections were determined by high performance liquid chromatography with electrochemical detection. Dopamine and NA had the same regional distribution; their concentrations were maximal near the prostatic end and decreased towards the epididymis. The concentration of 5-HT also decreased from the prostatic to the epididimal end, but 5-HT did not follow the same regional distribution as DA and NA. Reserpine (0.02 or 0.2 mg/kg, i.p., 24 hr) and 6-hydroxydopamine (2×80 mg/kg, i.v., 6 days) decreased the contents of DA and NA; the concentrations of both amines were modified to a similar extent. Reserpine also diminished the content of 5-HT. Pargyline (200 mg/kg, i.p., 2 hr) increased the concentration of 5-HT whilep-chlorophenylalanine (300 mg/kg, oral, 3 days) decreased the contents of the amine in some sections of the vas deferens. This study suggests that DA and NA co-exist in the same sympathetic neurons. Some of the 5-HT could be stored in mast cells as previously proposed, but the finding that tissue content of 5-HT changes after inhibiting the deamination or synthesis of the amine suggests that other source(s) of 5-HT distinct from mast cells exist in the rat vas deferens.     

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.     

Diurnal alterations of catecholamines, indoleamines and their metabolites in specific brain regions of the mouse

1. The diurnal variations of regional brain concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and metabolites were determined in unperturbed male CD-1 mice. Determinations were made every 4 hr for 24 hr. 2. The most striking and significant variations in biogenic amines were seen in the hypothalamus, where concentrations of NE, DA and 5-HT varied in a rhythmic pattern and as much as two-fold during this period. 3. In some cases, daily alterations in parent biogenic amines were reflected by concurrent changes in their metabolites. 4. Since concentrations of neurotransmitters in the brain are often used as an indicator of stress and/or toxicity, these data should provide an accurate data base allowing for more accurate interpretation of results.     

REGIONAL DISTRIBUTION OF MONOAMINES AND THEIR METABOLITES IN THE HUMAN BRAIN

Abstract— Noradrenaline (NA), dopamine (DA). 5-hydroxytryptamine (5-HT), 4-hydroxy, 3-methoxy-phenylethylene glycol (MHPG), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindolylacetic acid (5-HIAA) were measured in twenty areas of post-mortem brain from ten psychiatrically and neurologically normal patients. There was a marked difference, which did not appear to be related to sex, medication, cause of death or time between death and dissection, in amine and metabolite concentrations between brains. In the cortex, 5-HT, MHPG, HVA. DOPAC and S-HIAA were approximately even in their distribution; NA and DA could not be detected. In sub-cortical areas there were clear differences in the distribution of the three amines accompanied by less marked differences in the distribution of their respective metabolites.     

HPLC-EC analysis of catechols and indoles in rat brain dialysates

This short article reviews HPLC-EC methodology that we are currently applying to measure DA, 5-HT and their acid metabolites in rat brain dialysates collected in vivo. HPLC-EC systems based on standard-bore HPLC columns are described which are sufficiently sensitive to allow detection of the monoamine transmitters and their metabolites in regional brain dialysates collected at 10-20 min intervals. A large reduction in sample requirement was achieved by "down-scaling" the conventional HPLC-EC assay to incorporate small-bore HPLC columns. The small-bore systems allowed monoamines to be detected in samples collected over 1 to a few minutes.     

Serotonin, dopamine, noradrenaline and their metabolites: levels in the brain of the house cricket (Acheta domesticus L.) during a 24-hour period and after administration of quipazine--a 5-HT2 receptor agonist.

1. The levels of 5-HT, DA, NA and DA metabolites (NADA, DOPAC) measured by HPLC (with electrochemical detection) in the brain of the house cricket did not change over a 24-hr period. The level of 5-HIAA, a 5-HT metabolite, was below the limit of detection. 2. The 5-HT and DOPAC levels decreased and NADA increased after quipazine injection but DA and NA levels did not change after it. 3. [3H]Ketanserin was used to identify serotonin receptors bound to sites in the house cricket brain with a KD of 5 nM and a concentration of Bmax 180 fmol/mg protein.     

Immunocytochemical evidence for biogenic amines and immunogold labeling of serotonergic synapses in tentacles of Aiptasia pallida (Cnidaria, Anthozoa)

Abstract. Evidence for classical neurotransmitters in sea anemones remains controversial. We used high performance liquid chromatography with electrochemical detection (HPLC-EC) and electron microscopical imunocytochemistry to determine the presence of serotonin and precursor synthetic enzymes of other biogenic amines in tentacles of the sea anemone Aiptasia pallida. Using HPLC-EC we found dopamine and serotonin (5-hydroxytryptamine, 5-HT) in both tentacles and whole animal homogenates. Antibodies to tyrosine hydroxylase, dopamine β-hydroxylase, phenylethanolamine N-methyltransferase, and 5-HT were used with the peroxidase-antiperoxidase method to reveal positive immunoreactivity to these substances in neurons of tentacles. Immunogold labeling of serial thin sections with the anti-5–HT antibody revealed reactive products in synaptic vesicles at interneuronal, neuromuscular, and neurospirocyte synapses. These results suggest that both catecholamine and indolamine neurotransmitters occur in sea anemones in addition to the neuropeptide Antho-RFamide, indicating the presence of multiple types of transmitter substances in an early nervous system.     

Effect of intracerebroventricularly administered insulin on brain monoamines and acetylcholine in euglycaemic and alloxan-induced hyperglycaemic rats.

There is now conclusive evidence for the presence of insulin and insulin receptors in the mammalian CNS and it has been postulated that they can modulate peripheral glucose homeostasis. Since a number of central neurotransmitters are also known to influence glucose levels and it is likely that CNS insulin receptors act through neurotransmitter mediation, the present study was conducted to investigate the effect of intracerebroventricularly (icv) administered insulin on rat brain dopamine (DA), noradrenaline (NA), serotonin and acetylcholine (ACh) activity in normal and alloxan-induced hyperglycaemic animals. Insulin was administered in doses (50 and 100 microU) which induced minimal hypoglycaemia, so as to obviate the likely effects of hypoglycaemia on neurotransmitter function. DA was estimated in midbrain-diencephalon (MD) and caudate nucleus (CN), NA and serotonin in MD and pons-medulla (PM), while ACh was estimated in all the three areas, namely, MD, CN and PM. The regional brain concentrations of DA, NA and serotonin were more in the hyperglycaemic rats as compared to their euglycaemic counterparts. However, the reverse was noted in case of ACh. Insulin induced a decrease in rat brain DA and NA levels, which was more marked in the hyperglycaemic animals. Conversely, insulin induced an increase in rat brain serotonin concentration which was not significantly different in normal and hyperglycaemic rats. Insulin induced marked increase in rat brain ACh levels, which was accentuated in hyperglycaemic animals. The present study reports for the first time the likely interaction between CNS insulin receptors and brain monoamines, and ACh, in euglycaemic and hyperglycaemic states.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neocortical Dialysate Monoamines of Rats After Acute, Subacute, and Chronic Liver Shunt

Abstract: Intracerebral microdialysis was applied to monitor the neocortical extracellular levels of the aromatic amino acids phenylalanine, tyrosine, and tryptophan, the neurotransmitters dopamine (DA), noradrenaline (NA), and serotonin (5-HT), and the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid (5-HIAA) in rats with various forms of experimental hepatic encephalopathy (HE). The extracellular aromatic amino acid levels were clearly increased in acute, subacute, and chronic HE. No changes compared with controls in the neocortical DA release could be detected in the three experimental HE rat models investigated. The NA release showed a significant increase only in the subacute HE group. These data suggest that HE may not be associated with any major reduction of neocortical DA or NA release as previously suggested. In acute and subacute HE, decreased extracellular DOPAC but elevated 5-HIAA concentrations were seen. In chronic HE, elevations of both DOPAC and 5-HIAA were observed. Neocortical 5-HT release did not change in subacute and chronic HE, whereas it decreased in acute HE compared with control values. Significant increase in extracellular concentrations of 5-HIAA and of the 5-HIAA/5-HT ratio in the present study are in agreement with previously reported increases in 5-HT turnover in experimental HE. However, a substantially increased 5-HT turnover in experimental HE does not appear to be related to an increase in neuronal neocortical 5-HT release.     

Effect of various insecticides on the larval growth and biogenic amine levels of Tribolium castaneum Herbst

Various insecticides reduced larval growth of the red flour beetle (tribolium castaneum Herbst) and various biogenic amines, including octopamine (OA), dopamine (DA), serotonin (5-HT), epinephrine (E), norepinephrine (NE), their precursors and metabolites in the insects were measured by high-performance liquid chromatography coupled with electrochemical detection. Tyrosine occurred in the highest concentration followed by OA, tryptophan and 3,4-dihydroxymandelic acid (DOMA). Tyramine (a precursor of OA in the biosynthetic pathway), synephrine (N-methyl OA), DA, 5-HT, E, NE and their related substances occurred in extremely low quantities compared with OA. The insects were stressed by various insecticides, which resulted in a dramatic change of biogenic amine levels: the OA levels increased, whereas the levels of other biogenic amines and related substances decreased.     

Effect of the enterotropic carcinogen 1,2-dimethylhydrazine on the level of biogenic amines in the hypothalamus of rats]

The hypothalamic levels of noradrenaline (NA), dophamine (DA), serotonine (5-HT), 5-hydroxyindolacetic acid (5-HIAA) were found to be decreased in male rats 24 hours after subcutaneous injection of 1,2-dimethylhydrazine (SDMH) in a dose of 21 mg/kg. During 3 to 12 hrs after the SDMH treatment the hypothalamic level of NA was decreased, whereas the 5-HT turnover became greater. The hypothalamic histamine level increased 30 min after the SDMH injection only. In the brain stem and the great hemispheres the biogenic amine level displayed no significant changes under the effect of SDMH. The endocrine-metabolic changes due to the selected SDMH effect on the hypothalamic biogenic amine level are supposed to be of great significance in the realization of the carcinogenic action of SDMH in rats.     

Alternating extremely low frequency magnetic field increases turnover of dopamine and serotonin in rat frontal cortex

The aim of this study was to evaluate the influence of an extremely low frequency sinusoidal magnetic field (ELF MF) with frequency of 10 Hz and intensity of 1.8-3.8 mT on the levels of the biogenic amines dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), 5-hydroxytryptamine (5-HT), 5-hydroxyindolacetic acid (5-HIAA), and noradrenaline (NA), as well as on DA and 5-HT turnover in corpus striatum and frontal cortex of adult male Wistar rats. We found that ELF MF exposure for 14 days, 1 h daily, did not influence the level of the examined biogenic amines and metabolites, but increased the rate of synthesis (turnover) of DA and 5-HT in rat frontal cortex as compared to control, sham exposed rats. On the basis of the present results and our previous findings, extremely low frequency magnetic field (ELF MF) exposure has been found to alter both turnover and receptor reactivity of monoaminergic systems, as well as some behaviors induced by these systems or their agonists and antagonists.     

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.     

Post-mortem changes of neurotransmitter concentrations in the rat brain regions

Using High Performance Liquid Chromatography coupled with electrochemical detection the post-mortem stability of noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxy indole acetic acid (5-HIAA) were examined in the rat hypothalamus, amygdala, cerebral cortex, cerebellum and corpus striatum over an 8 hour time period. Changes in concentrations of the different neurotransmitters were less than it might be expected. The significant changes were: a. A fall in NA levels in the cerebral cortex by 4 hours and in the hypothalamus at 8 hours. b. A reduction in DA concentrations in the corpus striatum at 8 hours but a two fold rise of levels in the hypothalamus at 1 and 2 hours. c. A four-fold increase in 5-HT concentrations in the amygdala throughout the 8 hours studied. The results indicate that for comparative studies on post-mortem brain tissue correction factors should be employed to take into account differential changes in the concentrations of the various neurotransmitters.     

Changes in the Turnover of Monoamines in Prefrontal Cortex of Rats Fed on Vitamin E-Deficient Diet

Turnover of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites has been measured after a 15-day vitamin E-deficient diet in adult rat prefrontal cortex. Turnover rates of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxy-3-indoleacetic acid have been assayed from the disappearance rates after blocking by pargyline inhibition of monoamine oxidase. NA, DA, and 5-HT turnover rates have been measured as accumulation rates of NA, DA, and 5-HT after pargyline inhibition of monoamine oxidase. No change was found in the turnover rate of NA between control and experimental animals. In contrast, turnover rates of DA and homovanillic acid significantly increased in the animals fed on a low-vitamin E diet. However, the most striking results were found on the serotoninergic system. Levels of 5-HT and its main metabolite, 5-hydroxy-3-indoleacetic acid, and their respective turnover rates were lower in the vitamin E-deficient diet. These results could indicate that vitamin E is necessary for the normal functioning of the serotoninergic neurons in the rat prefrontal cortex. The involvement of vitamin E in preventing the formation of free radicals is well known. Therefore, this lack of protective effect after a 15-day vitamin E-deficient diet could be responsible for the neuronal damage to the serotoninergic system. The opposing results found in DA (increase) and 5-HT (decrease) turnover could provide further evidence for an inhibitory control of the serotoninergic ascending pathways to the dopaminergic system in the prefrontal cortex.