In vivo determination of endogenous biogenic amines in rat brain using HPLC and push-pull cannula.
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5-Hydroxytryptophan↗
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Prenatal stress: effects on brain biogenic amine and plasma corticosterone levels.
Pregnant rats were subjected to once daily stress treatments consisting of handling and a saline injection. The offspring showed region-specific changes in brain 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) levels in infancy but only the hypothalamus still showed significant changes at 60 days of age. In a reaction-to-stress test 23-day-old offspring in the prenatal stress group showed a greater elevation in plasma corticosterone level but smaller changes in hypothalamic NE and 5-HIAA levels than control offspring suggesting that prenatal stress may have altered the functioning of the hypothalamic-pituitary-adrenal axis. It is suggested that changes in the development of specific monoamine-containing neurons may be associated with the reported behavioral deficits in offspring of female rats stressed during pregnancy.
Animals↗
The development of brain biogenic amines, cyclic nucleotides and hyperactivity in 6-OHDA-treated rat pups.
Developmental changes in the behavior and brain biochemistry of rat pups were investigated in rats administered intracisternal injections of 6-hydroxydopamine (6-OHDA) or its vehicle at 5 days of age. Although pups of both groups were equivalent in their activity at 15 days of age, 6-OHDA-induced hyperactivity emerged at 20 and 30 days of age in a between-group design in which rats were only tested at one age. Body weight measurements revealed that 6-OHDA-treated rats were underweight at 15, 25 and 30 days of age. Furthermore, at 20 days of age, total activity was inversely related to body weights in the 6-OHDA-treated pups. Whole-brain levels of dopamine (DA) were decreased at every age by the 6-OHDA treatment, whereas norepinephrine (NE) levels were virtually unaffected by 6-OHDA at these same ages. Total activity was inversely correlated with whole-brain DA levels at 20 and 30 days of age when 6-OHDA-treated pups were hyperactive. Measures of cerebellar and "rest-of-brain" adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) were not uniformly altered by either the 6-OHDA treatment or by maturation. Results are discussed both in terms of brain biochemistry modulation of hyperactivity and the contribution of decreased body weights induced by 6-OHDA to the production of hyperactivity.
Aging↗
Effects of piracetam on retention and biogenic amine turnover in albino rats.
The chronic effects of orally administered 2-pyrrolidone acetamide (piracetam) on one-trial, passive avoidance task were studied in albino rats. The effects on the contents of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in the brain and on the levels of their metabolites both in the brain and urine were also assessed. Significant improvement was observed in the retention ability compared with saline-administered controls. The contents of NE, DA, and 5-HT and their metabolites in the brain were significantly decreased after piracetam administration. The urinary metabolite levels were also significantly decreased except total 3-methoxy-4-hydroxyphenyl glycol (MHPG). These data indicate that piracetam causes an overall decrease in the turnover of central monoamines. Thus, the results of this study implicate the involvement of NE, DA, and 5-HT systems in learning and memory processes. Piracetam did not exert any GABAergic effect as shown by the absence of change in the brain GABA levels.
Animals↗
Effects of leptophos on rat brain levels and turnover rates of biogenic amines and their metabolites.
Leptophos is a potent acetylcholinesterase inhibitor which causes delayed central-peripheral neuropathy. Rats were administered multiple doses of leptophos until motor deficits were observed in rotorod performance in the highest dosage group. Doses lower than the median effective dose were then administered to other rats and alterations of brain catecholamine and serotonin levels and turnover rates were determined. Turnover rates of brain norepinephrine and dopamine were elevated in rats administered cumulative doses of 75 mg/kg leptophos over a 15-day period. Levels of the major dopamine metabolite, 3,4-dihydroxyphenylacetic acid, appeared to be slightly elevated at this dose level and levels of dopamine were also higher than controls. These observations suggest that leptophos increases brain adrenergic activity. Rats administered the same dose levels had significantly reduced serotonin turnover rates. This observation was possibly artifactual, because rats administered a cumulative dose of 225 mg/kg leptophos showed no difference from controls.
Animals↗
Factors affecting the stability and separation of biogenic amines and their metabolites. Simultaneous measurement by HPLC with electrochemical detection.
We describe a simple and sensitive method for the rapid and simultaneous quantification of dopamine, 3-methoxytyramine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, serotonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan in the picogram range in small samples of brain tissue. After minimal sample preparation the amines were analyzed utilizing isocratic separation and reversed-phase high-performance liquid chromatography with amperometric detection. The effects of pH and methanol concentration in the solvent on the retention times of the amines on two different C-18 columns were investigated. Stabilities of the amines in solution were determined under various conditions. Light and air were found to be detrimental to the stability of indoles. In the absence of light, their stability was dependent on temperature and the presence of air; however, in the absence of air, light and/or temperature had little effect. The catechols were stable under most of these conditions. The assay has been applied to study the postmortem stability of dopamine, serotonin, and their metabolites in the striatum of rat brain. In the striatum 4 hr after death, the content of dopamine and 3,4-dihydroxyphenylacetic acid decreased by less than 20%, and 3-methoxytyramine increased by 158%, with no changes in serotonin, 5-hydroxyindoleacetic acid, and homovanillic acid.
Animals↗
Physical and chemical considerations in the in vitro calibration of microdialysis probes for biogenic amine neurotransmitters and metabolites.
The object of the present study was to examine the effects of temperature, oxidation, and pH on in vitro relative recovery of catecholamine and indoleamine neurotransmitters and their metabolites using microdialysis probes. Relative recovery of norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5HIAA), dopamine (DA), homovanillic acid (HVA), and 5-hydroxytryptamine (5HT) increased with temperature from 0 to 46 degrees C. For each compound, the increase in the amount recovered with increasing temperature was different. The stability of norepinephrine and dopamine was not affected at any temperature using deoxygenated calibration standard solutions containing ascorbic acid but was greatly reduced when exposed to ambient air without antioxidant treatment; catecholamine metabolites and the indole compounds were less affected. No change for in vitro relative recovery was observed by varying the pH of the perfusing solution from 6 to 8. Thus, temperature control in probe calibration as well as analyte stability using antioxidant treatment are important in reducing the error when estimating extracellular concentrations of neurotransmitter and metabolites.
Animals↗
Effects of ECT on sleep and CSF biogenic amines in affective illness.
The effects of electroconvulsive therapy (ECT) on sleep and cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were studied in 11 male patients suffering from major depressive disorders severe enough to require ECT. Total sleep time and sleep efficiency index increased significantly after ECT, while the number of awakenings, the ratio wake/total sleep time, and the time of intermittent awake decreased, indicating that sleep continuity improved after treatment. Sleep architecture was also favorably influenced by ECT as shown by a significant increase in time of stage 2 and rapid eye movement (REM) sleep. REM latency and REM density also normalized after ECT. CSF 5HIAA increased significantly after ECT, but this was not the case for CSF HVA. These results demonstrate a positive effect of ECT on sleep EEG and CSF neurochemical markers for depressive illness.
Adult↗
Effects of monoamine oxidase A inhibition on plasma biogenic amine metabolites in depressed patients.
The main metabolites of noradrenalin, dopamine, and serotonin-3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), respectively--were estimated in plasma of 21 depressed patients before and after 2 and 4 weeks of treatment with the monoamine oxidase-type A (MAO-A) inhibitor moclobemide (mean final daily dose = 8.9 mg/kg body weight). The treatment caused significant mean reductions in plasma MHPG and HVA (46% and 30%, respectively), while plasma 5-HIAA was unchanged. Multiple regression analysis revealed associations between reductions in MHPG and changes on the anxiety-somatization factor of the Hamilton Rating Scale for Depression (HRSD), and between reductions in HVA and changes in the HRSD factors cognitive disturbance and retardation.
Adult↗
Long-term consequences of prenatal cocaine exposure on biogenic amines in the brains of mice: the role of sex.
Prenatal cocaine exposure leads to multiple abnormalities in the mature offspring. We explored the effects of gestational exposure to cocaine on neurotransmitter systems of adult mice. The subjects were the mature offspring of mice (a) prenatally fed cocaine between gestational day (G) 8 and G19, (b) pair-fed chow and water, or fed chow and water ad libitum. The forebrains of the mature offspring were assayed for monoamines and amino acids. Cocaine exposure particularly affected the dopaminergic system and in a sex-specific manner. In males dopamine concentrations were decreased and dopamine turnover was increased, whereas in females dopamine concentrations were increased and turnover was decreased. Neither norepinephrine, the serotonergic system, nor neuroactive amino acids (or their precursors) were affected by cocaine. Thus, in utero exposure to cocaine produces long-lasting, specific defects in the dopaminergic system.
Amino Acids↗
Markers for biogenic amines in the aged rat brain: relationship to decline in spatial learning ability.
The major goal of the study was to evaluate the relationship of brain aging to individual differences in functional decline in rats. Forebrain choline-acetyltransferase (ChAT) and monoamines, including their metabolites, were examined in young and aged male Long-Evans rats in relation to their spatial learning ability. Aged rats that were unimpaired on a spatial learning task exhibited few changes in neurochemistry relative to the young group: each change in this subgroup was also evident in the remaining aged animals that were behaviorally impaired. Additional changes in neurochemical measures only found in the behaviorally impaired aged animals included decreased ChAT in the basal forebrain, striatum, and frontal cortex. A cluster analysis using the 15 neurochemical measures that were sensitive to aging yielded groupings of aged animals that differed with respect to their spatial learning ability, but not in their cue learning latencies. In this analysis the activity of ChAT in the basal forebrain and striatum appeared to be the best predictors of spatial learning impairment.
Aging↗
The effect of age, sex, weight and height on the plasma concentrations in healthy subjects of the acidic metabolites of some biogenic monoamines involved in psychiatric and neurological disorders.
1. The plasma concentrations of unconjugated phenylacetic acid and m-hydroxyphenylacetic acid are lower in male than in female subjects. 2. The plasma concentrations of unconjugated phenylacetic acid and mandelic acid decrease with increasing weight and height for all subjects combined. The same relationships apply for both males and females but are significant only for males. 3. Homovanillic and vanillylmandelic acid concentrations in plasma increase with age. 4. The importance of using age, sex, weight and height matched groups in studies involving the plasma concentrations of some of the trace amine metabolites in psychiatric disorders has been demonstrated. This is particularly the case for phenylacetic acid, the major metabolite of phenylethylamine which is now thought to be a neuromodulator of catecholaminergic neurotransmission.
Adult↗
The effect of the MAO-A selective inhibitor brofaromine on the plasma and urine concentrations of some biogenic amines and their acidic metabolites in bulimia nervosa.
1. Brofaromine or placebo were administered to female bulimia nervosa patients over a period of eight weeks. Plasma and urinary trace amines, their acidic metabolites and the acidic metabolites of the catecholamines and serotonin were assessed prior to treatment and at four and eight weeks after commencement of treatment. 2. The levels of both plasma and urinary homovanillic and vanilmandelic acids declined significantly during the first four weeks of treatment with brofaromine and then partially recovered to pre-drug levels by the eighth week. 5-Hydroxyindoleacetic acid levels were not affected by drug treatment at the times assessments were made. Urinary tryptamine increased significantly during the first four weeks of brofaromine treatment then partially recovered towards pre-drug levels by the eighth week. No effect from placebo treatment was observed.
Biogenic Amines↗
Biogenic amine metabolites in delusional (psychotic) depression and melancholia subtypes of major depression.
1. The levels of the urinary main metabolites of norepinephrine 3-methoxy-4-hydroxyphenylglycol (MHPG), of dopamine homovanillic acid (HVA) and of serotonin 5-hydroxyindoleacetic acid (5-HIAA) were measured in 84 patients with major depressive disorder, 34 delusional and 50 nondelusional. Melancholia subtype was also defined (N = 62). 2. MHPG was significantly higher in the delusional depressed group (p = 0.023). Female patients with delusional major depression also had significantly higher HVA excretion than female patients with non delusional major depression (p = 0.036). 5-HIAA excretion was similar in the two patient subgroups. 3. No significant differences in the three monoamine metabolites were found between the melancholic and nonmelancholic depressed patients.
Biogenic Amines↗
Association of biogenic amine metabolites with symptomatology in delusional (psychotic) and nondelusional depressed patients.
1. The levels of the main norepinephrine, serotonin, and dopamine metabolite excretion in the urine, MHPG, 5HIAA and HVA respectively, were measured in 84 patients with major depressive disorder, 34 delusional (psychotic) and 50 nondelusional (DSM-III-R criteria). 2. Associations with the 17 items of the HDRS were evaluated using the multiple regression analysis model. In the delusional group, MHPG excretion was positively related to the scores in the items of depressed mood (p = 0.04), middle insomnia (p = 0.008) and genital symptoms (p = 0.001). 5HIAA excretion was negatively associated with late insomnia (p = 0.02), work and interests (p = 0.001) and genital symptoms (p = 0.007). HVA was positively related to agitation (p = 0.043). In the nondelusional group the only association found was between agitation and HVA excretion (p = 0.03).
Adult↗
Regional alterations of brain biogenic amines in young rats following chronic lead exposure.
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Animals↗
Effect of chronic consumption of methylparathion on rat brain regional acetylcholinesterase activity and on levels of biogenic amines.
Wistar rat pups (female) were exposed to methylparathion (MPTH) by gastric intubation in single doses, or in a chronic regimen of different durations. A single dose of 1 mg MPTH/kg body weight in 15-day-old pups caused a significant decrease of acetylcholinesterase (AChE) activity in cerebellum (CE), motor cortex (MC) and brain stem (BS). The effect began to appear in about 20 min after administration, the peak effect was attained in 120 min and later on this waned off completely by 24 h. The effect was similar in young (15 days) and in adult (70 days) rats. A single dose of 0.2 mg MPTH/kg in 15 day old pups caused a reduction of AChE activity only in the BS, while a 0.1 mg MPTH/kg single dose given to 15-day-old pups caused no effect even in seven regions of the brain examined. Effect of low dose chronic administration of MPTH on AChE activity was also studied in CE, MC, BS, hippocampus (HI), striatum-accumbens (SA), spinal cord (SC) and also in the hypothalamus (HY). Administration of 0.1 mg MPTH/kg from second day to 15 days of age caused significant reduction of AChE activity in only 2 of the 7 brain regions studied. Administration of double the dose (0.2 mg MPTH/kg) and for a longer duration (2nd day to 150 days of age), caused a depression in all the brain regions studied. In all these regions, the levels of NA, DA and 5HT did practically not change. The results suggest that chronic consumption of MPTH leads to a moderate decrease of AChE activity in several brain regions.
Acetylcholinesterase↗
Localization of biogenic amines in Schistosoma mansoni.
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5-Hydroxytryptophan↗