Brain Amines Research Articles

The effect of in vivo deprenyl on cerebral amine system in rats with portocaval shunts.

Fig. 1. The effect of deprenyl treatment on brain amine system in portocaval shunted (PCA) rats. The data are given as means ± SEM for groups of 5‐7 rats. The results have been normalised to the values for non drug treated animals (100%). 5-HIAA-5-hydroxyindoleacetic acid; 5HT-serotonin; NA: noradrenaline; DA-dopamine; HA: histamine Statistical significance: * p < 0.05 ** p < 0.01 *** p < 0.001. A. HYPOTHALAMUS

Ectopic G-protein expression in dopamine and serotonin neurons blocks cocaine sensitization in Drosophila melanogaster.

Sensitization to repeated doses of psychostimulants is thought to be an important component underlying the addictive process in humans [1] [2] [3] [4]. In all vertebrate animal models, including humans [5], and even in fruit flies, sensitization is observed after repeated exposure to volatilized crack cocaine [6]. In vertebrates, sensitization is thought to be initiated by processes occurring in brain regions that contain dopamine cell bodies [2] [7]. Here, we show that modulated cell signaling in the Drosophila dopamine and serotonin neurons plays an essential role in cocaine sensitization. Targeted expression of either a stimulatory (Galpha(s)) or inhibitory (Galpha(i)) Galpha subunit, or tetanus toxin light chain (TNT) in dopamine and serotonin neurons of living flies blocked behavioral sensitization to repeated cocaine exposures. These flies showed alterations in their initial cocaine responsiveness that correlated with compensatory adaptations of postsynaptic receptor sensitivity. Finally, repeated drug stimulation of a nerve cord preparation that is postsynaptic to the brain amine cells failed to induce sensitization, further showing the importance of presynaptic modulation in sensitization.

Addiction to Oestrogen and Progesterone

Exogenous oestrogens, progesterone and progestogens are prescribed for a variety of conditions in spite of lack of proof of efficacy. Supraphysiological levels of oestrogen and progesterone have occurred in some individuals due to demands for increased doses. Brain function, amine metabolism and nutritional status can be altered by exposure to exogenous hormones. Direct and indirect mechanisms of psychoactivity may induce dependency. A doctor's severe 'menopausal type' withdrawal symptoms after exposure to oral conjugated oestrogens (Premarin 625 mu g/day) are reported.

Amine precursor therapy: manipulation of brain amine activity with precursor amino acid.

Amine precursor therapies for the treatment of neuropsychiatric disorders and their neurochemical background are reviewed historically. Furthermore, peculiar or artificial amino acids, which are metabolized into the brain amines or their derivatives and promised their clinical application of treatment for morbid conditions, are also introduced.

The role of tryptophan in DON-induced feed rejection.

Deoxynivalenol (DON, vomitoxin) commonly produced by Fusarium fungi can alter feeding behaviour of pigs and other farm animals. The effects of dietary tryptophan (TRP, precursor of brain amine serotonin) in combination with DON were examined in mice to determine if TRP can modulate DON toxicity. Results indicated that brain TRP can be influenced by dietary TRP, but no evidence of TRP potentiating DON toxicity was observed. Higher TRP levels likely induced amino acid imbalance leading to weight gain suppression.

Effects of Fluoxetine and Maprotiline on Functional Recovery in Poststroke Hemiplegic Patients Undergoing Rehabilitation Therapy

In animals, drugs that increase brain amine concentrations influence the rate and degree of recovery from cortical lesions. It is therefore conceivable that antidepressants may influence outcome after ischemic brain injury in humans. We evaluated the effects of the norepinephrine reuptake blocker maprotiline and the serotonin reuptake blocker fluoxetine on the motor/functional capacities of poststroke patients undergoing physical therapy. Fifty-two severely disabled hemiplegic subjects were randomly assigned to three treatment groups; during 3 months of physical therapy, patients were treated with placebo, maprotiline (150 mg/d), or fluoxetine (20 mg/d). Before and at the end of the observation period, we assessed activities of daily living by the Barthel Index, degree of neurological deficit by a neurological scale for hemiplegic subjects, and depressive symptomatology by the Hamilton Depression Rating Scale. The diverse treatments ameliorated walking and activities of daily living capacities to different extents. The greatest improvements were observed in the fluoxetine-treated group and the lowest in the maprotiline-treated group. Furthermore, fluoxetine yielded a significantly larger number of patients with good recovery compared with maprotiline or placebo. These effects of the drugs were not related to their efficacy in treating depressive symptoms. Fluoxetine may facilitate or, alternatively, maprotiline may hinder recovery in poststroke patients undergoing rehabilitation. The effects of fluoxetine as an adjunct to physical therapy warrant further investigation, since treatment with fluoxetine may result in a better functional outcome from stroke than physical therapy alone.

Amine precursor amino acid therapy: from neurochemical basis to clinical aspects.

The particulars regarding the amine precursor therapy for treatment of neuropsychiatric disorders and their neurochemical background are described historically. Furthermore, peculiar or artificial amino acids which are metabolized into the brain amine or their derivatives and promised their clinical application are also introduced.

Regulation of pyridoxal-5'-phosphate level by biogenic amines in mouse brain.

We investigated the relationship between the concentration of pyridoxal-5'-phosphate (PLP) and biogenic amine in mouse brain. The production of PLP from pyridoxal (PL) by pyridoxal kinase (PLK) was inhibited by the addition of dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT), but not by that of epinephrine and N-acetyl-serotonin. DA and NE were combined with PLP by a non-enzymatic reaction, whereas 5-HT was bound only slightly with PLP. The conjugated product of PLP with DA was also detected by HPLC analysis when PLK activity was assayed using PL as a substrate in the presence of DA. In an in vivo investigation, the depletion of DA and 5-HT in mouse brain after an intraperitoneal injection of 5 mg/kg reserpine, led to slight elevation of the PLP level to 120% of the control level. By contrast, the increase in DA in the brain caused by intraperitoneal administration of 150 mg/kg L-DOPA caused the PLP concentration to decrease to 70% of the control level. However, no change in PLK activity in the brain was observed when the mice were treated with either reserpine or L-DOPA. These results suggested that the level of PLP in mouse brain was partly regulated by the concentration of biogenic amines, such as DA, NE and 5-HT, without apparent induction of PLK.

Effects of carbon dioxide on levels of biogenic amines in the brains of queenless worker and virgin queen honey bees (Apis mellifera)

SUMMARYSeveral experiments were conducted to examine the effects of exposure to CO2 or CO2 containing 20% O2 on the amounts of biogenic amines in the brain, and on development of ovaries in worker and queen honey bees. When workers were fed pollen and exposed to CO2, their ovaries were less developed and brain dopamine (DA), tryptophan (TRP) and tyrosine (TYR) levels were significantly reduced versus untreated controls that were also fed pollen. If workers were not fed pollen and exposed to CO2, the differences in brain amine content between untreated controls and CO2-treated workers were not significant; however, a significant reduction in brain TRP and TYR levels through time was found for both groups of workers. Treatment with CO2 stimulated free-running queens to lay eggs sooner than untreated free-running queens, but CO2 narcosis had no significant affect on queen brain chemistry. However, the brain chemistry of caged queens (many queens caged within a single colony) responded differently from free-r...

1‐Benzyl‐1,2,3,4‐Tetrahydroisoquinoline as a Parkinsonism‐Inducing Agent: A Novel Endogenous Amine in Mouse Brain and Parkinsonian CSF

1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) was detected as a novel endogenous amine in mouse brain and parkinsonian CSF by using the gas chromatography-selected ion-monitoring method. The level of 1BnTIQ was very high in CSF of some parkinsonian patients compared with that of controls with other neurological diseases, the mean value being three times higher (parkinsonians: 1.17 +/- 0.35 ng/ml of CSF, n = 18; vs. controls: 0.40 +/- 0.10 ng/ml of CSF, n = 11; mean +/- SEM, not significantly different). The pole test, a toxicological examination to evaluate behavior abnormalities related to Parkinson's disease, was used to examine the pharmacological effect of 1BnTIQ in mice. Repeated administration of 1BnTIQ induced behavior abnormalities, which pretreatment with 1-methyl-1,2,3,4-tetrahydroisoquinoline could prevent. We suggest that 1BnTIQ may be related to the idiopathic Parkinson's disease.

Effect of dexfenfluramine on metabolic and neurochemical measures in restraint-stressed ob/ob mice

Genetically obese (ob/ob) and lean C57BL/6J mice were subjected to 1 h acute restraint stress, and the effects on plasma glucose and corticosterone, and brain amines, were assessed relative to nonrestrained groups. Some mice were treated with dexfenfluramine (DFEN) prior to restraint. Compared with their lean counterparts, ob/ob mice had elevated basal plasma levels of both glucose and corticosterone. Both lean and ob/ob showed comparable absolute resraint-induced increments in these measures, but the fractional increase was much smaller in ob/ob. Metabolism of NE, DA and 5-HT was also assessed from the ratio of the metabolite-to-amine in various brain regions. Obese mice had smaller restraint-related increases in monoamine metabolism than lean their counterparts. Acute DFEN increased corticosterone, but tended to reduce the restraint-induced elevations in glucose and monoamine metabolism.

In memory to Ye. V. Naumenko

On November 13, 1994, science suffered a heavy loss - an outstanding Russian scientist, professor, doctor of medical sciences, the founder of a number of original directions in world neuroendocrinology Evgeny Vladimirovich Naumenko prematurely passed away. In the 60s, the scientific interests of E.V. Naumenko were focused on studying the role of biogenic brain amines in the neurochemical regulation of the hypothalamic-pituitary-adrenocortical system. In particular, he proved for the first time that one of the final hypothalamic neural pathways stimulating the synthesis and secretion of corticoliberin is serotonergic in nature. The results of these widely known studies at home and abroad brought well-deserved fame to a neuroendocrinologist from Siberia. In the last 20 years, the main work of E.V. Naumenko concerned the study of genetic evolutionary and ontogenetic aspects of stress, the role of neuroendocrine mechanisms in animal domestication processes, the role of neurochemical brain mechanisms in the dominant behavior of individuals in micropopulations, and the study of a new model of hereditary arterial hypertension. Professor E.V. Naumenko has published over 300 works, including more than a dozen major monographic publications published at home and abroad. These publications are widely known among specialists, they have made a significant contribution to the development of neuroendocrinology and brought well-deserved recognition to their author.

In memory to Ye. V. Naumenko

On November 13, 1994, science suffered a heavy loss - an outstanding Russian scientist, professor, doctor of medical sciences, the founder of a number of original directions in world neuroendocrinology Evgeny Vladimirovich Naumenko prematurely passed away. In the 60s, the scientific interests of E.V. Naumenko were focused on studying the role of biogenic brain amines in the neurochemical regulation of the hypothalamic-pituitary-adrenocortical system. In particular, he proved for the first time that one of the final hypothalamic neural pathways stimulating the synthesis and secretion of corticoliberin is serotonergic in nature. The results of these widely known studies at home and abroad brought well-deserved fame to a neuroendocrinologist from Siberia. In the last 20 years, the main work of E.V. Naumenko concerned the study of genetic evolutionary and ontogenetic aspects of stress, the role of neuroendocrine mechanisms in animal domestication processes, the role of neurochemical brain mechanisms in the dominant behavior of individuals in micropopulations, and the study of a new model of hereditary arterial hypertension. Professor E.V. Naumenko has published over 300 works, including more than a dozen major monographic publications published at home and abroad. These publications are widely known among specialists, they have made a significant contribution to the development of neuroendocrinology and brought well-deserved recognition to their author.

An antibody to agmatine localizes the amine in bovine adrenal chromaffin cells

Agmatine, a newly identified amine in mammalian brain, is an endogenous ligand for imidazoline and α 2-adrenergic receptors. We sought to develop a polyclonal antibody to agmatine suitable for immunocytochemistry. Agmatine was conjugated to keyhole limpet hemocyanin and injected into rabbits. The polyclonal antiserum so generated dose-dependently recognized the agmatine conjugate but not carrier protein by dot blot. Its reaction with the conjugate was selectively antagonized by agmatine but not related compounds. The antiserum, but not pre-immune or pre-adsorbed antiserum, selectively stained cultured adrenal chromaffin cells. Our results indicate that agmatine immunoreactivity is contained in a sub-population of adrenal chromaffin cells and, thus, these antibodies are useful for immunocytochemical localization of the amine in mammalian tissues.

Stimulatory effect of octopamine on juvenile hormone biosynthesis in honey bees ( Apis mellifera): Physiological and immunocytochemical evidence

The effect of octopamine on the activity of corpora allata of adult worker honey bees has been examined in vitro and correlated to the local distribution of this biogenic amine in brain and retrocerebral complex as studied immunocytochemically by means of an highly specific antiserum. Octopamine causes a dose-dependent increase in juvenile hormone release from corpora allata. Maximum increase is obtained with concentrations of 10 −6 M in nurse and foraging bees by 45.3 or 32.3%, respectively. Octopamine-like immunoreactivity occurs in about 45 somata of the median neurosecretory cells in the pars intercerebralis of the bee brain. They project via immunopositive nervus corporis cardiaci I into the corpora cardiaca, where interspersed varicose structures and 8–10 cell bodies in the ventral part of this gland are stained. A network of immunoreactive fine varicose nerve fibres surrounds each gland cell of the corpora allata. Immunoreactivity in these neuronal structures is detectable if bees were starved over night, a condition in which corpora allata elicit the highest juvenile hormone production ever observed in bees. Both, the stimulatory effect of octopamine and the presence of immunoreactive nerve fibers in the corpora allata, strongly indicate a physiological role of this biogenic amine in the regulation of juvenile hormone biosynthesis in adult honey bees.

Lesions of central serotonin systems affect responding on a progressive ratio schedule reinforced either by intravenous cocaine or by food

The effect of intraventricular infusions of the serotonergic neurotoxin, 5,7-dihydroxytrytamine (5,7-DHT), was examined in rats trained on a progressive ratio schedule for either IV cocaine or food reinforcement. Animals in the 5,7-DHT treatment group responded to significantly higher breaking points than vehicle-injected control animals, regardless of whether food or cocaine was used as the reinforcing stimulus. Analysis of the regional brain amines indicated that depletions of mesencephalic 5-HT correlated with postsurgical alterations in responding. These findings suggest that depletion of forebrain 5-HT produces a general effect on responding rather than a specific alteration in the reinforcing effects of psychomotor stimulant drugs.

Central catecholamine alterations induced by stressor exposure: analyses in recombinant inbred strains of mice

Stressors increase plasma corticosterone concentrations and the turnover of norepinephrine (NE) and dopamine (DA) in some brain regions. However, appreciable interindividual and interstrain differences exist in this respect. The present investigation assessed the NE and DA changes induced by uncontrollable footshock in the BALB/cByJ and C57BL/6ByJ mice and seven recombinant inbred strains. Stressor exposure indeed provoked strain dependent alterations of plasma corticosterone, hypothalamic and mesocortical NE, as well as mesocortcolimbic DA. The profile of stressor effects in the recombinant strains with respect to the NE alterations, the mesocortical DA changes, as well as plasma corticosterone was commensurate with a polygenic mode of inheritance. The data were related to behavioral changes induced by stressors in these strains of mice, as well as to the contribution of the brain amines to stressor-induced behavioral changes.

Effects of ethanol on brain monoamine content of spontaneously hypertensive rats (SHR).

Spontaneously hypertensive rats (SHR) were administered either 2.4 g/kg ethanol or an isocaloric glucose daily for 4 weeks and the levels of norepinephrine (NE), epinephrine (EP), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in different brain regions were determined. Results indicated a 3-fold increase in NE level in brain stem and hypothalamus and more than 2-fold increase in DA in corpus striatum in alcohol-treated rats as compared to controls. There was a significant increase in the level of DA in the corpus striatum but the levels in cerebral cortex, brain stem and hippocampus were decreased instead. Decreases in 5-HT levels were found in hypothalamus, brain stem, cortex and cerebellum of alcohol-treated brain as compared to untreated controls. These results indicate alterations of the biogenic amine contents in different regions of the SHR brain after chronic ethanol ingestion. Since stimulated release of biogenic amines in the SHR brain has been implicated in the regulation of blood pressure, changes due to ethanol ingestion may be a risk factor in hypertensive patients.

The potentiation of cortical neuron responses to noradrenaline by 2-phenylethylamine is independent of endogenous noradrenaline.

2-Phenylethylamine (PE) is an endogenous brain amine which produces sympathomimetic responses and potentiates cortical neuron responses to noradrenaline (NA). In order to examine further the mechanism of action of PE, extracellular recordings were made of the activity of single neurones in the cerebral cortex in urethane-anesthetized rats. Sympathomimetic responses to PE were blocked by pretreatment with reserpine, reserpine plus alpha-methyl-p-tyrosine and desipramine. It is concluded that the sympathomimetic responses to PE are indirect. 2-Phenylethylamine potentiated cortical neuron responses to electrical stimulation of the locus coeruleus in a dose-dependent manner. This was seen when PE was given systemically (with as little as 1 microgram/kg) and iontophoretically. The effects of PE were not reproduced by its metabolite phenylacetic acid or its putative metabolite phenylethanolamine. Iontophoretic applications of PE (0-6 nA, 2-5 minutes) potentiated cortical neuron responses to iontophoretically applied NA, without affecting the spontaneous firing rate, or the responses to iontophoretically applied GABA or acetylcholine. This effect of PE was not blocked by pretreatment with alpha-methyl-p-tyrosine or desipramine, and was potentiated by pretreatment with reserpine and reserpine plus alpha-methyl-p-tyrosine. It is probable that the ability of PE to modulate neuronal responses to NA does not involve the presynaptic NA terminal or endogenous NA and it is likely that PE acts directly to increase the efficacy of NA. These findings are consistent with the hypothesis that the physiological role of PE is to modulate catecholaminergic transmission within the central nervous system.

Alterations in extracellular and tissue levels of biogenic amines in rat brain induced by the serotonin2 receptor antagonist, ritanserin.

Systemic administration of ritanserin elicited rapid changes in dopamine (DA) and serotonin (5-HT) levels in both dialysate and neuronal tissue extracts. These effects occurred in both a site-selective and a dose-related manner. Increases in extracellular levels of DA and 5-HT in the nucleus accumbens were maximal at 120-140 min after treatment. A dose of 0.63 mg/kg of ritanserin elicited larger and more prolonged increases in extracellular DA and 5-HT levels than did the 0.3 mg/kg dose. By contrast, 0.63 mg/kg of ritanserin elicited no changes in either DA or 5-HT levels with dialysate collected from the striatum. Ritanserin also induced dose-related decreases in tissue levels of DA and 5-HT from the nucleus accumbens. The site specificity of action was again noted in that there were no dose-dependent decreases in tissue levels of DA or 5-HT measured from the striatum. Ritanserin exerted little effect on metabolite levels from either dialysate or tissue extracts. Taken together, these findings show that selective 5-HT2 receptor antagonism modulates DA and 5-HT neurotransmission in a specific manner. These actions appear to involve increased release of DA and 5-HT rather than significant changes in metabolism. These findings add further weight to the importance of 5-HT2 receptor interactions as an important component of antipsychotic activity.