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Effects of growth hormone on brain biogenic amine levels.

The effects of IP administered bovine growth hormone (GH) on regional brain serotonin, 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine levels in rats were examined. GH decreased the levels of both monoamines and 5-HIAA in the diencephalon and brainstem while not affecting telencephalic concentrations. In hypophysectomized rats, however GH produced significant elevations of monoamine and 5-HIAA levels in all brain regions. In normal rats the decreases in norepinephrine content produced by GH were correlated with a reduction in the stimulatory action of d-amphetamine on general activity levels. These results demonstrate that GH can affect brain biogenic amines and that these effects have behavioral consequences.

Animals↗

Thyrotropin releasing hormone (TRH): DOPA potentiation and biogenic amine studies.

The present study in mice demonstrated the TRH when administered over 5 days remained active in the Everett Dopamine Potentiation Test. No evidence of tolerance was observed. In fact, an accumulative effect of TRH appeared to take place. Ablation of the adrenals, ovaries, testes, pineal, spleen, parathyroid, one kidney, or thymus did disrupt this behavioral potentiation of dopamine by TRH. TRH was found to potentiate the effects of imipramine. T3, T4, and TSH were found to be active in the DOPA potentiating test. No overt toxicity was observed between TRH and pargyline or between TRH and DOPA. Toxicity was seen only when all three agents were used together. TRH was found active in young and old mice. TRH was also found active in potentiating the central effects of serotonin. Biogenic amine brain levels in mice were not altered by TRH when administered for five days. Alpha-methyl-p-tyrosine reduced the activity of TRH in the dopamine potentiation test, suggesting dopaminergic mechanisms are involved by a direct receptor interaction.

5-Hydroxytryptophan↗

Phencyclidine: effects on motor activity and brain biogenic amines in the guinea pig.

Previous reports suggesting that the behavioral response of the guinea pig to phencyclidine (PCP) administration is more similar to the effects of PCP observed in higher animals than those observed in mice and rats prompted us to investigate the effects of PC on spontaneous motor activity and brain biogenic amine levels in the guinea pig. Doses of 2.5 and 5.0 mg/kg PCP were found to significantly elevate spontaneous motor activity; however, 7.5 mg/kg PCP produced highly variable results which were not significantly different from control. The concentrations of tryptophan, serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were measured in the forebrain and hindbrain of previously drug naive animals 30 min after administration of 5 mg/kg PCP. As compared to saline injected control animals, PCP was observed to have no effect on any of the neurochemical determinants measured. Contrary to previous reports, these data suggest that PCP produces behavioral effects in the guinea pig which are not unlike those observed in mice and rats. Furthermore, the effects which we report on spontaneous motor activity are not related to changes in the regional concentration of any of the neurochemical variables which were measured.

Animals↗

Recovery of memory following forgetting induced by depletion of biogenic amines.

Following depletion of biogenic amines by reserpine, mice were trained to avoid one compartment of a shuttle box by employing the procedures of Pavlovian fear conditioning. Retention was tested one week later using both an active and a passive measure. A robust amnesia was apparent in reserpine-treated animals on both retention measures. Treatment with the mixed dopamine-serotonin agonist lisuride 30 min prior to the test alleviated the memory loss. Since improved retention in the drug treated mice was indexed by increased response latencies in the passive test and decreased latencies in the active test it is unlikely that the improvement in performance was the result of non-specific effects on activity. The results are consistent with the hypothesis that lisuride treatment before testing facilitates retrieval processes.

Animals↗

Chlordiazepoxide, go-nogo successive discrimination and brain biogenic amines in cats.

Chlordiazepoxide (CDP; 0.4 mg/kg/day, per os) was administered to cats during either the acquisition (CDP 21-22 days) of a go-nogo successive discrimination task (SD) or the performance (CDP 10 days) of the previously learned SD task. Endogenous levels of serotonin, 5-hydroxyindoleacetic acid, noradrenaline and dopamine were assayed in 12 brain areas, in trained as well as in untrained cats. This study has shown that (1) CDP strongly impaired the acquisition but not performance of the SD task, revealing a dissociation of the effects of CDP on these two stages of training; (2) the CDP administration, as well as the SD training, produced regional changes in brain levels of biogenic amines, suggesting the involvement of particular monoaminergic neurons in the behavioral effects of CDP and in operant behavior; and (3) in particular brain areas, interactions were observed between the effects of the SD training and those of the CDP administration on monoamines, indicating that the behavioral state may interfere with the neurochemical effects of CDP.

Animals↗

Selection for growth alters the feeding response to injections of biogenic amines.

Two experiments were conducted to determine if selection for growth altered the response to intracerebroventricular (ICV) injections of methoxamine and 5-hydroxytryptamine (5-HT). Lines of chickens divergently selected over 25 generations for 8-week body weight were used. The ICV injection of methoxamine into fully fed birds significantly increased food intake in the high-weight line but had no effect on food intake in the low-weight line. Conversely, the ICV injection of 5-HT had no effect in fully fed birds but significantly decreased food intake in 24-hr fasted birds in both weight-lines. Food intake was affected by 5-HT for a much longer period in the high-weight line than in the low-weight line. These results suggest that selection for growth alters the brain response to biogenic amines.

Animals↗

A rapid and simple HPLC microassay for biogenic amines in discrete brain regions.

A rapid microassay is described for the measurement of biogenic amines using an isocratic HPLC system with electrochemical detection. Catecholamines, indoleamines and their major metabolites were extracted with 150 microliters of perchloric acid from brain tissue punches (less than 250 micrograms) using a simple one-step sample preparation method. These compounds were separated on a short (80 mm) column with 3 microns particle size packing, and electrochemically detected within a total run time of less than 6 minutes. Detection limit sensitivity was approximately 2-5 pg. This method, detailed in an easy-to-follow description, reduces assay time, minimizes the possibility for errors, maximizes efficiency, and requires only standard HPLC equipment and supplies.

Animals↗

MDMA transiently alters biogenic amines and metabolites in mouse brain and heart.

(+-)-3,4-Methylenedioxymethamphetamine (MDMA) (10, 20, and 40 mg/kg) was administered to male CF-1 mice which were sacrificed 3, 6, or 24 hours posttreatment for analysis of brain and cardiac biogenic amines and metabolites. In contrast to reported effects of MDMA in the rat, the highest dose of MDMA transiently elevated mouse brain 5-hydroxytryptamine (5-HT) 3 hours following drug treatment. Levels of dopamine were not significantly affected. 5-Hydroxyindoleacetic acid and dihydroxyphenylacetic acid were significantly lowered by MDMA at the two early time points. The highest dose of MDMA produced a transient depletion of norepinephrine in mouse brain and heart tissue. Only the effects of MDMA on cardiac norepinephrine were prevented by pretreatment of animals with desipramine. A regimen consisting of four daily doses of 40 mg/kg MDMA only produced significant declines in 5-HIAA, dopamine and homovanillic acid levels one week following the last dose. These data confirm previous reports that mice are resistant to the neurotoxic effects of MDMA suggesting that a species variation in response to MDMA exists.

3,4-Methylenedioxyamphetamine↗

Effects of hemivibrissotomy in the rat: time-dependent asymmetries in turning and biogenic amines induced by apomorphine.

Behavioral and neurochemical changes accompanying unilateral removal of vibrissae were investigated in the rat. Rats were tested either 4 hours or 10 days after hemivibrissotomy. A systemic injection of apomorphine (0.5 mg/kg) induced turning behavior towards the intact vibrissae side in rats tested 4 hours after hemivibrissotomy. Compared to these animals, apomorphine induced more turning towards the side of vibrissae removal and less turning towards the intact side in animals tested 10 days after vibrissae removal. This reversal is suggestive of time-dependent changes in dopamine receptor sensitivity. Analysis of biogenic amines (dopamine, norepinephrine, serotonin) in the hemispheres ipsi- and contralateral to the side of vibrissae removal revealed evidence for neurochemical changes in apomorphine- and amphetamine-treated rats. Lateralized and bilateral differences were found in the neostriatum, septum and ventral mesencephalon, which were dependent on the side and duration of hemivibrissotomy. These results are discussed with respect to the behavioral and neural analogy between hemivibrissotomy and unilateral 6-hydroxydopamine lesions of the nigrostrial system.

Amphetamine↗

Behavioral concomitants of regional changes in the brain's biogenic amines after apomorphine and amphetamine.

Behavioral and neurochemical changes were analyzed in rats after systemical injections of the dopamine receptor agonist apomorphine (0.5 mg/kg) or the indirect agonist amphetamine (1.0 mg/kg). As expected, amphetamine led to an increase in locomotion, whereas apomorphine resulted in decreases in locomotion, rearings, and grooming. The analysis of biogenic amines in tissue samples showed that amphetamine decreased 3,4-dihydroxy-phenylacetic acid (DOPAC) levels and DOPAC/dopamine ratios in the neostriatum, and resulted in a lower 5-hydroxyindole-3-acetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the ventral mesencephalon. Apomorphine decreased the dopamine metabolites [DOPAC, homovanillic acid (HVA), 3-methoxy-tyramine (3-MT)] and their respective metabolite/transmitter ratios and increased dopamine levels in the neostriatum. Similar decreases in dopamine metabolites or their ratios were found in the ventral mesencephalon, septum, and frontoparietal cortex but not the thalamus. In addition to its effects on dopamine, apomorphine decreased norepinephrine in the ventral neostriatum and 5-HT and 5-HIAA in the cortex. Correlations between behavioral activity and neurochemical metabolism (using the metabolite-transmitter ratios for the latter) revealed relationships between locomotion and serotonergic activity in the thalamus of animals treated with amphetamine. Evidence for a relationship between locomotion or rearings and dopaminergic activity was found in all six brain areas analyzed. Here, the pattern of correlation was dependent on the kind of treatment and the behavioral and neurochemical measures. These results support earlier findings on the neurochemical effects of apomorphine and amphetamine in the neostriatum and ventral mesencephalon, and add new evidence for an action on the septal area, thalamus, and frontoparietal cortex.

Amphetamine↗

Longitudinal study of inmates of a prison for the psychiatrically disturbed: plasma concentrations of biogenic amine metabolites and amino acids.

Plasma concentrations of eight large and neutral amino acids and 10 acidic metabolites of biogenic amines in seven inmates incarcerated in the Regional Psychiatric Centre (Praries), Correctional Service of Canada, were assessed each week day for 4 weeks (i.e., 20 samples each). Measures of central tendency and dispersion of the variables were calculated. The measures are distinctively different in their variability and their normality of distribution. The large and neutral amino acid (LNAA) measures are somewhat less variable, but also less likely to be normally distributed than most acid metabolites. Acid metabolites tend to show consistent interindividual differences that persist over time, with the notable exception of 5-hydroxyindoleacetic acid. LNAA measures tend to show differences across time but not between individuals. The distributional properties of LNAA measures are largely accounted for by the observation of a downward convergence of values of these variables over the 4 weeks of the study.

Adult↗

Biogenic amines and adenosine-sensitive adenylate cyclases in primary cultures of striatal neurons.

Primary cultures of virtually pure striatal neurons from 16-day-old mouse embryos can be obtained using a serum-free chemically defined medium. Membranes prepared from these cells contain dopamine, beta-adrenergic, serotonin and adenosine sensitive adenylate cyclases. The pharmacological properties of the dopamine receptors are similar to those found for D1 receptors in adults except for the apparent affinities for agonists which were 5-10 times higher in fetal neurons. Beta-adrenergic receptors of striatal and cerebellar fetal neurons are of the beta 1-subtype as indicated by their identical affinity for adrenaline and noradrenaline and by their homogeneous, high affinity for practolol (Ki = 1.3 X 10(-6)M). Adenosine and serotonin sensitive adenylate cyclases present classical characteristics. An extensive study of the additive effects of the 4 neurotransmitter-sensitive adenylate cyclases indicates that: (1) part of the neurons bear more than one type of biogenic amine receptors; (2) the serotonin receptors are always associated with adenosine receptors on the same neurons; (3) adenosine- and dopamine-sensitive adenylate cyclases are additive. From this it can be concluded that as far as their adenylate cyclases-linked amine receptors are concerned, a maximal number of 15 types of neurons are present in these striatal cell cultures.

Adenosine↗

Increased biogenic amine release in mouse hypothalamus following immunological challenge: antagonism by indomethacin.

Stimulation of the acute-phase response in mice by lipopolysaccharide, pokeweed mitogen, concanavalin A or interleukin-1 was associated with increased release of biogenic amines, serotonin and norepinephrine in the hypothalamus as indexed by their primary metabolites, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol, respectively. The increases in norepinephrine and serotonin turnover observed 4 h following systemic administration of interleukin-1 were antagonized by concurrent administration of indomethacin, a potent inhibitor of cyclooxygenase. These data suggest that the increase in norepinephrine and serotonin release in mouse hypothalamus during the acute-phase response to infection is partially mediated by the actions of arachidonic acid metabolites.

Animals↗

The change with age in biogenic amines and their metabolites in the striatum of the rat.

The changes in the content of the biogenic amines and their metabolites in the striatum of the rat during the aging period (3-30 months) have been studied. The maximum levels of dopamine (DA) have been found at 6 months of age and this concentration is maintained until 24 months. Between 24 to 30 months there is a decrease in the concentration of this compound. At that time, there is a slight increase in 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) concentration, the main metabolites of DA, which suggests a slight increase in DA metabolism. The 3-methoxytyramine (3-MT) concentration also increases at this time. The maximum concentration of noradrenaline (NA) was also found at 6 months of age. Tryptophan has the maximum concentration after DA and this is maintained over the life-span of the rat. The concentration of serotonin (5-HT) is high and does not change during this period. However, the concentration of 5-HT, as occurred with DA, decreased between 24 and 30 months. Also the DA/5-HT ratio does not change during the period studied.

3,4-Dihydroxyphenylacetic Acid↗

Biogenic amines: their importance in foods.

Biogenic amines are important nitrogen compounds of biological importance in vegetable, microbial and animal cells. They can be detected in both raw and processed foods. In food microbiology they have sometimes been related to spoilage and fermentation processes. Some toxicological characteristics and outbreaks of food poisoning are associated with histamine and tyramine. Secondary amines may undergo nitrosation and form nitrosamines. A better knowledge of the factors controlling their formation is necessary in order to improve the quality and safety of food.

Bacteria↗

Effect of trimipramine, an atypical tricyclic antidepressant, on the activities of various enzymes involved in the metabolism of biogenic amines.

1. The mechanism of action of trimipramine, a clinically efficacious tricyclic antidepressant, is not well understood. In order to investigate whether it might affect the activities of different enzymes involved in biogenic amine metabolism we have undertaken a comparative study of it along with amitriptyline. 2. Neither trimipramine nor amitriptyline, at concentrations up to 1 mM, exhibited any significant effect on phenylalanine hydroxylase, tyrosine hydroxylase, L-aromatic amino acid decarboxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyltransferase, catechol-O-methyltransferase, phenylsulfotransferase or tyrosine aminotransferase. 3. Monoamine oxidase, however, was inhibited by both drugs with the greatest effect being on MAO-B. The inhibition was reversible, non-competitive and relatively weak.

Adrenal Glands↗

Counteraction of the genotoxicity of some cooked-food mutagens by biogenic amines.

The biogenic amines tryptamine, 5-hydroxytryptamine, tyramine and histamine were assessed for their abilities to modify the genotoxicity of the cooked-food mutagens IQ, MeIQ, MeIQx, Trp-P-1 and Trp-P-2. These measurements were made using a bacterial mutation assay with hepatic fractions from either SWR mice or DSN Syrian hamsters as the activating system and Salmonella typhimurium TA98 as the indicator organism. Although histamine had very little effect on the genotoxicity of these mutagens, the other amines reduced genotoxicity, with tryptamine and 5-hydroxytryptamine exerting the greatest effect. Generally the amines exhibited greater potency when S-9 fractions from mice rather than from hamsters were used.

Animals↗

Effect of formamidines on 5-hydroxytryptamine uptake and biogenic amine levels in rat platelets.

Uptake of radioactive 5-hydroxytryptamine (5-HT) by platelets from rats treated intraperitoneally with the insecticide/acaricide chlordimeform (CDF) at 25 mg/kg was not significantly influenced at 1 h; however, uptake of this amine by platelets from rats treated with its N- monodemethyl metabolite (DMC) at the same dosage was significantly inhibited (37%). Two reversed phase high performance liquid chromatographic systems with electrochemical detection were developed with a capacity to separate 11 biogenic amines and related compounds. Only 5-HT, norepinephrine (NE), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were consistently detected in platelets and plasma samples. At 1 h and/or 24 h postinjection, CDF effected significant decreases in platelet levels of 5-HT, NE, and DA and plasma levels of 5-HT, whereas platelet and plasma levels of DOPAC were significantly increased. DMC effected significant decreases in both platelet and plasma levels of 5-HT. These in vivo studies confirmed previous in vitro experiments which demonstrated that formamidines inhibited uptake of 5-HT by platelets and released endogenous stores of amines from platelets.

3,4-Dihydroxyphenylacetic Acid↗