Brain Biogenic Amines Research Articles

Comment on "Food wanting is mediated by transient activation of dopaminergic signaling in the honey bee brain".

Huang et al. (1) make an exciting claim about a human-like dopamine-regulated neuromodulatory mechanism underlying food-seeking behavior in honey bees. Their claim is based on experiments designed to measure brain biogenic amine levels and manipulate receptor activity. We have concerns that need to be addressed before broad acceptance of their results and the interpretation provided.

Cucurbita maxima Seeds Reduce Anxiety and Depression and Improve Memory.

The current study was planned to assess the neuropharmacological benefits of the Cucurbita maxima seed. These seeds have been conventionally used for the nutritional as well as amelioration of various diseases. However, there was a need to provide a pharmacological basis for such use. Four central nervous system-related functions, that is, anxiety, depression, memory, and motor coordination, were evaluated, and the levels of brain biogenic amines were also assessed. Anxiety was evaluated through selected experimental models, such as light and dark apparatus, elevated plus maze, head dip, and open field test. The head dip test was mainly used to assess exploratory behavior. Depression was assessed by two animal models, that is, the forced swim test and tail suspension test. Memory and learning ability were assessed by the passive avoidance test, stationary rod apparatus, and Morris's water maze test. Motor skilled learning was assessed by stationary rod and rotarod apparatus. Reversed phase high-pressure liquid chromatography was used to determine biogenic amine levels. Results reveal that C. maxima exhibited anxiolytic and antidepressant effects with memory improvement. There was a reduction in the weight of the animal following chronic administration. Furthermore, no remarkable effects were observed on motor coordination. Norepinephrine was found elevated, which may be linked to its antidepressant effects. These biological effects of C. maxima may be due to the presence of secondary metabolites, such as cucurbitacin, beta-sitosterol, polyphenolic compounds, citrulline, kaempferol, arginine, β-carotene, quercetin, and other antioxidants. The outcomes of the present study authenticate that the chronic use of C. maxima seeds reduces the intensity of neurological problems like anxiety and depression.

The role of C1473G polymorphism in triptophanhydroxylase-2 gene in the acute ethanol effects on <i>c-fos</i> gene expression and metabolism of biogenic amines in brain of mice

Tryptophan hydroxylase-2 is a key enzyme in the synthesis of the neurotransmitter serotonin, which plays an important role in the mechanisms of regulation of a wide range of physiological functions and behaviors. In this work, we studied the effect of acute ethanol administration on the expression of the c-fos early response gene and the metabolism of serotonin and catecholamines in the brain structures of B6-1473C and B6-1473G congenic mice, which differ in the C1473G single-nucleotide substitution in the Tph2 gene and enzyme activity. Acute alcoholization led to a significant increase in c-fos gene expression in the frontal cortex and striatum of B6-1473G mice and the hippocampus of B6-1473C mice. The introduction of ethanol caused a decrease in the index of serotonin metabolism in the nucleus accumbens in B6-1473C mice, as well as in the hippocampus and striatum of B6-1473G mice. Also, ethanol led to a decrease in the level of norepinephrine in the hypothalamus in B6-1473C mice. Thus, the C1473G polymorphism in the Tph2 gene has a significant effect on changes in the c-fos gene expression pattern and metabolism of biogenic amines in the brain induced by acute ethanol administration.

The Role of C1473G Polymorphism in Mouse Triptophan Hydroxylase 2 Gene in the Acute Effects of Ethanol on the c-fos Gene Expression and Metabolism of Biogenic Amines in the Brain

Tryptophan hydroxylase 2 is a key enzyme in the synthesis of the neurotransmitter serotonin, which plays an important role in the regulation of behavior and various physiological functions. We studied the effect of acute ethanol administration on the expression of the early response c-fos gene and metabolism of serotonin and catecholamines in the brain structures of B6-1473C and B6-1473G congenic mouse strains differing in the single-nucleotide substitution C1473G in the Tph2 gene and activity of the encoded enzyme. Acute alcoholization led to a significant upregulation of the c-fos gene expression in the frontal cortex and striatum of B6-1473G mice and in the hippocampus of B6-1473C mice and caused a decrease in the index of serotonin metabolism in the nucleus accumbens in B6-1473C mice and in the hippocampus and striatum of B6-1473G mice, as well as to the decrease in the norepinephrine level in the hypothalamus of B6-1473C mice. Therefore, the C1473G polymorphism in the Tph2 gene has a significant effect of acute ethanol administration on the c-fos expression pattern and metabolism of biogenic amines in the mouse brain.

The Geomagnetic Field (GMF) Is Necessary for Black Garden Ant (Lasius niger L.) Foraging and Modulates Orientation Potentially through Aminergic Regulation and MagR Expression.

The geomagnetic field (GMF) can affect a wide range of animal behaviors in various habitats, primarily providing orientation cues for homing or migratory events. Foraging patterns, such as those implemented by Lasius niger, are excellent models to delve into the effects of GMF on orientation abilities. In this work, we assessed the role of GMF by comparing the L. niger foraging and orientation performance, brain biogenic amine (BA) contents, and the expression of genes related to the magnetosensory complex and reactive oxygen species (ROS) of workers exposed to near-null magnetic fields (NNMF, ~40 nT) and GMF (~42 µT). NNMF affected workers' orientation by increasing the time needed to find the food source and return to the nest. Moreover, under NNMF conditions, a general drop in BAs, but not melatonin, suggested that the lower foraging performance might be correlated to a decrease in locomotory and chemical perception abilities, potentially driven by dopaminergic and serotoninergic regulations, respectively. The variation in the regulation of genes related to the magnetosensory complex in NNMF shed light on the mechanism of ant GMF perception. Overall, our work provides evidence that the GMF, along with chemical and visual cues, is necessary for the L. niger orientation process.

Effects of Sex and Group Size on Behavior and Brain Biogenic Amines in Short-Lived Turquoise Killifish (Nothobranchius furzeri).

Short-lived turquoise killifish (Nothobranchius furzeri) becomes a popular model species for neuroscience. However, the effects of sex and rearing conditions on behavior and brain monoamines in N. furzeri are unknown. In this article, we study the body mass, behavior in the novel tank diving test, levels of noradrenaline (NA), dopamine (DA), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) in the brain of 108 day-old N. furzeri males and females reared in small (one male and one or two females in 4-L tanks) and large (four males and four females in 25-L tanks) groups. Males were heavier and had a lower NA level in the brain compared with females. The behavior of males and females did not differ in the novel tank diving test. Their DA, 5-HT, DOPAC, and 5-HIAA levels in the brain did not differ too. Males from small groups spent more time near the tank's bottom. Rearing in small groups reduced the DA level in the female brain and the DOPAC level in female and male brains. However, group size did not affect body mass, 5-HT and 5-HIAA levels in the brain. Thus, group size is important for behavior and neuroscience studies of N. furzeri.

Semax, synthetic ACTH(4–10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats

Selective serotonin reuptake inhibitors (SSRI) are commonly used to treat depression during pregnancy. SSRIs cross the placenta and may influence the maturation of the foetal brain. Clinical and preclinical findings suggest long-term consequences of SSRI perinatal exposure for the offspring. The mechanisms of SSRI effects on developing brain remain largely unknown and there are no directional approaches for prevention of the consequences of maternal SSRI treatment during pregnancy. The heptapeptide Semax (MEHFPGP) is a synthetic analogue of ACTH(4–10) which exerts marked nootropic and neuroprotective activities. The aim of the present study was to investigate the long-term effects of neonatal exposure to the SSRI fluvoxamine (FA) in white rats. Additionally, the study examined the potential for Semax to prevent the negative consequences of neonatal FA exposure. Rat pups received FA or vehicle injections on postnatal days 1–14, a time period equivalent to 27–40 weeks of human foetal age. After FA treatment, rats were administered with Semax or vehicle on postnatal days 15–28. During the 2nd month of life, the rats underwent behavioural testing, and monoamine levels in brain structures were measured. It was shown that neonatal FA exposure leads to the impaired emotional response to stress and novelty and delayed acquisition of food-motivated maze task in adolescent and young adult rats. Furthermore, FA exposure induced alterations in the monoamine levels in brains of 1- and 2- month-old rats. Semax administration reduced the anxiety-like behaviour, improved learning abilities and normalized the levels of brain biogenic amines impaired by the FA exposure. The results demonstrate that early-life FA exposure in rat pups produces long-term disturbances in their anxiety-related behaviour, learning abilities, and brain monoamines content. Semax exerts a favourable effect on behaviour and biogenic amine system of rats exposed to the antidepressant. Thus, peptide Semax can prevent behavioural deficits caused by altered 5-HT levels during development.

Long-term clinical outcome of 6-pyruvoyl-tetrahydropterin synthase-deficient patients

Introduction6-Pyruvoyl-tetrahydropterin synthase deficiency (PTPSd) is a rare autosomal recessive disorder of synthesis of biogenic amines, which is characterized by variable neurological impairment and hyperphenylalaninemia. We aimed to assess the long-term clinical outcome of this disorder and the factors affecting it. MethodsAt total of 28 PTPSd patients (aged 19.9 ± 10.9 years) underwent clinical (neurological and psychiatric) and neuropsychological assessment (BRIEF, VABS-II, and IQ). Based on CSF homovanillic (HVA) and 5-hydroxyindolacetic acid (5-HIAA) and pterin concentrations at diagnosis, patients were classified as having either a severe [SF; low level of CSF, HVA, and 5-HIAA with altered neopterin/biopterin (Neo/Bio)] or mild form (MF; normal HVA and 5-HIAA with altered Neo/Bio) of PTPSd. ResultsApproximately 36% of patients had MF PTPSd. At the last examination, 43% of patients had movement disorders (2 MF, 10 SF), 43% of patients had variable degrees of intellectual disability (SF only), 39% met the criteria for a psychiatric disorder (3 MF, 9 SF). Applying a linear regression model, we found that HVA and phenylalanine levels at birth had a significant influence on IQ, BRIEF, and VABS-II variability. Lastly, 5-HIAA further contributed to VABS-II variability. The disease showed a self-limiting clinical course and its treatment, although delayed, is effective in improving the neurological status. ConclusionsNeurodevelopmental impairment due to PTPSd shows a self-limiting course. A continuous improvement in the neurological condition has been observed in patients receiving treatment, even when delayed. The severity of brain biogenic amine depletion at diagnosis predicts neurological and psychiatric outcomes.

Brain Aminergic Deficiency in Absence Epileptic Rats: Dependency on Seizure Severity and Their Functional Coupling at Rest

Brain aminergic tone was examined in rats with different genetically determined generalized epilepsies and in normal rats. Our previously published database was analyzed to examine if there were functional correlations between brain biogenic amines and their metabolic rates within particular cerebral regions. Rats with genetically determined absence (AbS) and/or audiogenic seizures (AGS) served as models for human generalized non-convulsive and convulsive epilepsies. Tissue concentrations of 5-HT, dopamine (DA) and their main metabolites, as well as tryptophan (TRT), histamine (HA) and noradrenaline (NA) were assayed in different brain regions and analyzed for within-regions correlations in non-stressed conditions. It was found that AbS rats had higher indices of DA-ergic metabolism than non-epileptic controls, but the severity of AbS correlated with a widespread dopaminergic deficiency, as expressed in lowered indices of DA metabolism. AGS exerted no major effects on tissue neurochemistry. Brain DA-ergic and 5HT-ergic metabolic indices (measured as the ratio of the metabolite to the parent transmitter) were closely linked in striatum and pons-medulla of AbS rats. Remarkably, the tissue content of HA in pons-medulla of AbS rats displayed correlations with metabolic ratios of 5HT and DA, which was not seen in normal rats. It is hypothesized that enhanced metabolism of DA and 5HT are at least partial compensatory antiepileptic mechanisms in the brain, and a disturbance of this compensation leads to an aggravation of absence seizures.

Serotonergic control in initiating defensive responses to unexpected tactile stimuli in the trap-jaw ant Odontomachus kuroiwae.

The decision to express either a defensive response or an escape response to a potential threat is crucial for insects to survive. This study investigated an aminergic mechanism underlying defensive responses to unexpected touch in an ant that has powerful mandibles, the so-called trap-jaw. The mandibles close extremely quickly and are used as a weapon during hunting. Tactile stimulation to the abdomen elicited quick forward movements in a dart escape in 90% of the ants in a colony. Less than 10% of the ants responded with a quick defensive turn towards the source of stimulation. To reveal the neuronal mechanisms underlying this defensive behavior, the effect of brain biogenic amines on the responses to tactile stimuli were investigated. The levels of octopamine (OA), dopamine (DA) and serotonin (5HT) in the brain were significantly elevated in ants that responded with a defensive turn to the unexpected stimulus compared with ants that responded with a dart escape. Oral administration of DA and 5HT demonstrated that both amines contributed to the initiation of a defensive response. Oral administration of l-DOPA weakly affected the initiation of the defensive turn, while 5-hydroxy-l-tryptophan (5HTP) strongly affected the initiation of defensive behavior. Oral administration of ketanserin, a 5HT antagonist, inhibited the initiation of the defensive turn in aggressive workers, abolishing the effects of both 5HT and 5HTP on the initiation of turn responses. These results indicate that 5HTergic control in the nervous system is a key for the initiation of defensive behavior in the trap-jaw ant.

Influence of immobilization and forced swim stress on the neurotoxicity of lambda-cyhalothrin in rats: Effect on brain biogenic amines and BBB permeability

Experimental studies have been carried out on rats to understand the influence of immobilization stress (IMS), a psychological stressor and forced swim stress (FSS), a physical stressor in the neurotoxicity of lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid with extensive applications. No significant change in plasma corticosterone levels and blood brain barrier (BBB) permeability was observed in rats subjected to IMS (one session of 15min/day), FSS (one session of 3min/day) for 28days or LCT treatment (3.0mg/kg body weight, p.o. suspended in groundnut oil) for 3days (26th, 27th and 28th day) as compared to controls. Marginal changes in the levels of biogenic amines and their metabolites (NE, EPN, DA, HVA, DOPAC, 5-HT) in hypothalamus, frontal cortex, hippocampus, and corpus striatum were observed in rats subjected to IMS or FSS or LCT alone as compared to controls. It was interesting to note that pre-exposure to IMS or FSS followed by LCT treatment for 3days caused a marked increase in plasma corticosterone levels associated with disruption in the BBB permeability as compared to rats exposed to IMS or FSS or LCT alone. Pre-exposure to IMS or FSS followed by LCT treatment for 3days resulted to alter the levels of biogenic amines and their metabolites in hypothalamus, frontal cortex, hippocampus, and corpus striatum as compared to rats exposed to IMS or FSS or LCT alone. Although neurochemical changes were more intense in rats pre-exposed to IMS as compared to those subjected to FSS on LCT treatment, the results indicate that both psychological and physical stress could be important influencing factors in the neurotoxicity of LCT.

Young coconut water ameliorates depression via modulation of neurotransmitters: possible mechanism of action.

In the current era, plants are frequently tested for its antidepressant potential. Therefore young coconut water, a commonly used plant based beverage, was selected to explore its antidepressant potential. Rodents were selected for this study and forced swim test was conducted to explore antidepressant activity. Analysis of brain biogenic amines using high performance liquid chromatography coupled with electrochemical detection and potentiation of noradrenaline toxicity model were also incorporated in this study to demonstrate probable antidepressant mechanism of action. Coconut water was administered orally at the dose of 4ml/100g. Young coconut water showed highly significant increase in struggling time (p<0.001) in forced swim test. This suggests antidepressant effect of young coconut water. In noradrenaline toxicity model, it was observed that young coconut water is not a good adrenergic component as its lethality percentage in this test was observed 0% unlike imipramine which showed lethality of 100%. High performance liquid chromatography-electrochemical detection of rodent's brain revealed decline in 5-hydroxytryptamine, noradrenaline and dopamine, with concomitant decline in metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, homovanillic acid and increase in 5-hydroxyindoleacetic acid/5-hydroxytryptamine ratio. Findings from the exploration of monoamines suggest antidepressant effect of young coconut water via homeostasis of monoamines synthesis.

Physiology of reproductive worker honey bees (Apis mellifera): insights for the development of the worker caste.

Reproductive and behavioural specialisations characterise advanced social insect societies. Typically, the honey bee (Apis mellifera) shows a pronounced reproductive division of labour between worker and queen castes, and a clear division of colony roles among workers. In a queenless condition, however, both of these aspects of social organisation break down. Queenless workers reproduce, forage and maintain their colony operating in a manner similar to communal bees, rather than as an advanced eusocial group. This plasticity in social organisation provides a natural experiment for exploring physiological mechanisms of division of labour. We measured brain biogenic amine (BA) levels and abdominal fat body vitellogenin gene expression levels of workers in queenright and queenless colonies. Age, ovary activation and social environment influenced brain BA levels in honey bees. BA levels were most influenced by ovary activation state in queenless bees. Vitellogenin expression levels were higher in queenless workers than queenright workers, but in both colony environments vitellogenin expression was lower in foragers than non-foragers. We propose this plasticity in the interacting signalling systems that influence both reproductive and behavioural development allows queenless workers to deviate significantly from the typical worker bee reaction norm and develop as reproductively active behavioural generalists.

Correlated responses in death-feigning behavior, activity, and brain biogenic amine expression in red flour beetle Tribolium castaneum strains selected for walking distance.

Dispersal ability may influence antipredator and mating strategies. A previous study showed a trade-off between predation avoidance and mating success in strains of the red flour beetle Tribolium castaneum selected for walking distance . Specifically, beetles derived from strains selected for longer walking distance suffered higher predation pressure and had higher male mating success than their counterparts derived from strains selected for shorter walking distance. In the study reported here, we compared the locomotor activity, biogenic amine expression in the brain, and death-feigning behavior of the red flour beetle strains selected for walking distance. The results indicated that individuals genetically predisposed to longer walking distance had higher locomotor activity and lower intensity of death-feigning behavior than those genetically predisposed to shorter walking distance. However, no significant differences were found in the expression of biogenic amines in the brain among strains selected for walking distance, although the level of dopamine in the brain differed from that of the strains divergently selected for duration of death-feigning behavior. The relationships between walking speed, activity, death-feigning behavior, and brain biogenic amines in T. castaneum are discussed.

Changes in tissue oxidative stress, brain biogenic amines and acetylcholinesterase following co-exposure to lead, arsenic and mercury in rats

The present study investigated the toxic effects of individual, combined (binary and ternary) exposure to lead, arsenic and mercury on, (i) oxidative stress (ii) alterations in brain biogenic amines and (iii) tissue metals concentration. Rats were exposed to lead, arsenic and mercury either individually (30 ppm in drinking water), various binary (15 ppm each) or ternary combination (10 ppm each) for a period of 6 months. Lead + arsenic and lead + arsenic + mercury co-exposure led to a significant increase in the blood oxidative stress. Mercury + arsenic and lead + arsenic + mercury co-exposure produced a more pronounced hepatotoxicity while, lead + arsenic and lead + arsenic + mercury produced a significant increase in hepatic oxidative stress. Kidney oxidative stress and changes in brain biogenic amines were more prominent in animals exposed to three metals. Accumulation of three metals did not exhibit the pattern as in the case of oxidative stress. Exposure to two toxic metals also showed less accumulation of toxic metals suggesting possible antagonism. The present study thus provides some interesting observations on the interaction between lead, arsenic and mercury. Co-exposure to lead + arsenic + mercury led to a more pronounced increase in oxidative stress in liver and kidneys compared to other exposed groups.

Sodium tungstate induced neurological alterations in rat brain regions and their response to antioxidants

Tungsten, recognized recently as an environmental contaminant, is being used in arms and ammunitions as substitute to depleted uranium. We studied the effects of sodium tungstate on oxidative stress, few selected neurological variables like acetylcholinesterase, biogenic amines in rat brain regions (cerebral cortex, hippocampus and cerebellum) and their prevention following co-administration of N-acetylcysteine (NAC), naringenin and quercetin. Animals were sub-chronically exposed to sodium tungstate (100 ppm in drinking water) and orally co-supplemented with different antioxidants (0.30 mM) for three months. Sodium tungstate significantly decreased the activity of acetylcholinesterase, dopamine, nor-epinephrine and 5-hydroxytryptamine levels while it increased monoamine oxidase activity in different brain regions. Tungstate exposure produced a significant increase in biochemical variables indicative of oxidative stress while, neurological alterations were more pronounced in the cerebral cortex compared to other regions. Co-administration of NAC and flavonoids with sodium tungstate significantly restored glutathione, prevented changes in the brain biogenic amines, reactive oxygen species (ROS) and TBARS levels in the different brain regions. The protection was more prominent in the animals co-administered with NAC. We can thus conclude that sodium tungstate induced brain oxidative stress and the alterations in some neurological variables can effectively be reduced by co-supplementation of NAC.

Negative impact of manganese on honeybee foraging.

Anthropogenic accumulation of metals such as manganese is a well-established health risk factor for vertebrates. By contrast, the long-term impact of these contaminants on invertebrates is mostly unknown. Here, we demonstrate that manganese ingestion alters brain biogenic amine levels in honeybees and fruit flies. Furthermore, we show that manganese exposure negatively affects foraging behaviour in the honeybee, an economically important pollinator. Our findings indicate that in addition to its direct impact on human health, the common industrial contaminant manganese might also have indirect environmental and economical impacts via the modulation of neuronal and behavioural functions in economically important insects.

A high dose of short term exogenous d-galactose administration in young male rats produces symptoms simulating the natural aging process

Aimsd-Galactose (d-gal) induced accelerated senescence has been used to develop an aging model for brain. Previously, long term administration of a wide range of doses has been used for this purpose. In the present study we investigate whether short term administration of a high dose of d-gal in rats induces significant signs and symptoms similar to natural aging. Main methodsYoung rats were injected intraperitoneally with d-gal at a dose of 300mg/ml/kg for one week. Behavioral analysis for depression and anxiety like symptoms were monitored by forced swim test (FST) and light/dark transition (LDT) test. Assessment of memory was done using the Morris water maze (MWM), passive avoidance test (PAT) and elevated plus maze (EPM) test. Biochemical analysis was done for estimation of antioxidant enzymes and acetylcholinesterase. Determination of brain biogenic amines was performed by HPLC–EC. Key findingsShort term administration of d-gal significantly altered behavioral, biochemical and neurochemical responses in rats. d-Gal injected rats exhibited depressogenic and anxiogenic behaviors while memory was also significantly impaired in these rats. Brain lipid peroxidation and superoxide dismutase activity were significantly increased while catalase and glutathione peroxidase decreased. Increased activity of acetylcholinesterase was also exhibited by d-gal injected rats while brain biogenic amines were significantly decreased. Food intake and growth rate were however comparable in both groups. SignificanceTogether the behavioral, biochemical and neurochemical impairments following the high dose of d-gal suggest that symptoms similar to natural aging may be developed in rats in as early as one week.

Social dominance and reproductive differentiation mediated by dopaminergic signaling in a queenless ant.

In social Hymenoptera with no morphological caste, a dominant female becomes an egg layer, whereas subordinates become sterile helpers. The physiological mechanism that links dominance rank and fecundity is an essential part of the emergence of sterile females, which reflects the primitive phase of eusociality. Recent studies suggest that brain biogenic amines are correlated with the ranks in dominance hierarchy. However, the actual causality between aminergic systems and phenotype (i.e. fecundity and aggressiveness) is largely unknown due to the pleiotropic functions of amines (e.g. age-dependent polyethism) and the scarcity of manipulation experiments. To clarify the causality among dominance ranks, amine levels and phenotypes, we examined the dynamics of the aminergic system during the ontogeny of dominance hierarchy in the queenless ant Diacamma sp., which undergoes rapid physiological differentiation based on dominance interactions. Brain dopamine levels differed between dominants and subordinates at day 7 after eclosion, although they did not differ at day 1, reflecting fecundity but not aggressiveness. Topical applications of dopamine to the subordinate workers induced oocyte growth but did not induce aggressiveness, suggesting the gonadotropic effect of dopamine. Additionally, dopamine receptor transcripts (dopr1 and dopr2) were elevated in the gaster fat body of dominant females, suggesting that the fat body is a potential target of neurohormonal dopamine. Based on this evidence, we suggest that brain dopamine levels are elevated in dominants as a result of hierarchy formation, and differences in dopamine levels cause the reproductive differentiation, probably via stimulation of the fat body.

HPLC determination of brain biogenic amines following treatment with bispyridinium aldoxime K203

Effect of a new acetylcholine-esterase reactivator, K203 as a new potential antidote in organophosphate intoxications was studied on dopamine (DA), homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels in seven brain regions (cerebellum, spinal cord, hippocampus, hypothalamus, striatum, medulla oblongata and frontal cortex) of rats by an optimized and validated HPLC method. No significant change in brain level of these neurotransmitters was found either 15 or 60 min following treatment. However, when 5-HIAA/5-HT ratios were calculated as measure of turnover, significant decreases were found in the cerebellum, hippocampus, hypothalamus and the frontal cortex 15 min following K203 administration, but after 60 min only in the frontal cortex.