Catecholamines In Mouse Brain Research Articles

Effect of γ-ethyl-γ-phenyl-butyrolactone (EFBL), anticonvulsant and hypnotic drug, on mouse brain catecholamine levels

γ-Ethyl-γ-phenyl-butyrolactone (EFBL) is a structural combination of the anticonvulsant γ-hydroxy-γ-ethyl-γ-phenylbutyramide (HEPB) and the hypnotic γ-butyrolactone (GBL), which inherits both properties. To clarify its mechanism of action, the effects of EFBL, GBL and HEPB on dopamine (DA) and noradrenaline (NA) brain levels were investigated. Influences of chlorpromazine, phenelzine and aminooxyacetic acid were also studied. EFBL increased DA in a dose-dependent manner, remaining enhanced by 80 % over a period of 24 h and augmented NA by 54 % one hour after treatment. HEPB increased DA and NA approximately 2-fold after the first hour. GBL raised DA and NA after three and 24 h, resp. EFBL reversed chlorpromazine effects but potentiated those of phenelzine on DA. Amino-oxyacetic modified neither DA nor NA brain levels, not even in the presence of EFBL. The anticonvulsant and hypnotic properties of EFBL are attributed to its effect on presynaptic dopaminergic receptors and its lasting effect on ethyl and phenyl radicals that hinder its degradation. The results support the role of DA and NA in regulating seizure activity in the brain and indicate that EFBL offers a potential treatment for refractory epilepsy without complementary drugs and Parkinson's disease, without the drawbacks of oral therapies.

Effect of apomorphine and pimozide on synthesis and turnover of labelled catecholamines in mouse brain.

Journal Article Effect of apomorphine and pimozide on synthesis and turnover of labelled catecholamines in mouse brain Get access Henrik Nybäck, Henrik Nybäck Departments of Pharmacology, and Psychiatry (s:t Göran’s Hospital), Karolinska Institutet, S-104 01 Stockholm 60, Sweden Search for other works by this author on: Oxford Academic Google Scholar Johan Schubert, Johan Schubert Departments of Pharmacology, and Psychiatry (s:t Göran’s Hospital), Karolinska Institutet, S-104 01 Stockholm 60, Sweden Search for other works by this author on: Oxford Academic Google Scholar Göran Sedvall Göran Sedvall Departments of Pharmacology, and Psychiatry (s:t Göran’s Hospital), Karolinska Institutet, S-104 01 Stockholm 60, Sweden Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 22, Issue 8, August 1970, Pages 622–624, https://doi.org/10.1111/j.2042-7158.1970.tb10583.x Published: 12 April 2011 Article history Received: 08 April 1970 Published: 12 April 2011

Differential effects on mouse brain catecholamine turnover of chlorpromazine, trifluoperazine and closely-related non-tranquillizing analogues.

Differential effects on mouse brain catecholamine turnover of chlorpromazine, trifluoperazine and closely-related non-tranquillizing analogues.

Copper deficiency during neonatal development alters mouse brain catecholamine levels

Copper (Cu) deficiency was investigated in Swiss Webster albino mice to develop a model that alters brain catecholamine metabolism without serious growth impairment. Cu deficiency was induced by feeding a diet low in Cu (modified AIN-76A) to dams beginning either 7 days prior, 4 days prior, 4 days after, or on the day of parturition. Control dams were given Cu in the drinking water (20 μg Cu/mL); their pups were considered Cu-adequate (+Cu). Mice were weaned when three weeks old and were maintained on the treatment of their dams for an additional week. All four-week-old male Cu-deficient (−Cu) offspring exhibited biochemical characteristics of Cu deficiency when compared to their respective +Cu control mice. However, the best model, which resulted in altered catecholamine metabolism characterized by elevation of dopamine (DA) and depression in norepinephrine (NE) in brain and heart, was when treatment began 4 days prior to birth. Body and brain weight were not altered. However, levels of Cu in brain were markedly reduced to 21% of those measured in +Cu controls. Furthermore, brain NE and DA concentrations of −Cu mice were 72% and 132% of those quantified in +Cu offspring, respectively. Confirmatory studies demonstrated equivalent results in female offspring. One-month dietary Cu repletion studies reversed most biochemical changes in the “−Cu” mice. Brain Cu levels remained lower in repleted mice (55% of those in +Cu controls). These data and previous results support the hypothesis that neonatal Cu deficiency results in permanent changes to the brain.

Catecholamine uptake sites in mouse brain: distribution determined by quantitative [ 3H]mazindol autoradiography

Because of the importance of the mouse brain catecholamine system in the study of the neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) and because little information is available concerning the chemical neuroanatomy of the mouse, catecholamine uptake sites were mapped in C57 black mouse brain using [ 3H]mazindol autoradiography. Displacement studies with known dopamine (DA) and noradrenaline (NA) uptake blockers showed that binding in the striatum was entirely to DA uptake sites, while binding in the locus coeruleus was to NA uptake sites only. By using the selective noradrenergic uptake blocker desmethylimipramine (DMI), a complete map of both DA and NA uptake sites was generated. The mesostriatal DA system was the most clearly labelled and uptake sites were seen better in striatal terminals than the substantia nigra. Within the noradrenergic system, highest binding levels were seen over the locus coeruleus, although it was unclear whether these uptake sites were on cell bodies or terminals from the lateral tegmental noradrenergic system. These maps of the catecholamine uptake system in mouse brain provide a baseline for study of newly discovered neurotoxins and ageing processes.

Different effects of monoamine oxidase inhibition on MPTP depletion of heart and brain catecholamines in mice

Pargyline, an inhibitor of monoamine oxidase type B (MAO-B), did not prevent the depletion of heart norepinephrine 24 hr after a single dose of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in mice. In mice killed 24 hr after the last of 4 daily doses of MPTP, the depletion of dopamine in the striatum and of norepinephrine in the frontal cortex was completely prevented by pargyline, but the depletion of heart norepinephrine was not prevented. These results with pargyline are the same as results obtained earlier with deprenyl, another selective inhibitor of MAO-B. The doses of pargyline and of deprenyl that were used resulted in almost complete inhibition of MAO-B activity (phenylethylamine as substrate) in brain, heart and liver of mice. Deprenyl did not inhibit MAO-A activity (serotonin as substrate) in brain, but pargyline caused some inhibition of MAO-A in brain. In heart and liver, serotonin was oxidized only at about 1 10 the rate of phenylethylamine oxidation, suggesting that MAO-B predominates in these tissues. Both pargyline and deprenyl caused some inhibition of serotonin deamination in heart and liver, suggesting that the oxidation may have been due partly to MAO-B. Experiments with selective MAO inhibitors in vitro showed that only about 20% of the oxidation of serotonin was occuring via MAO-B in heart and liver. The in vitro oxidation of MPTP by MAO in mouse brain, heart and liver was almost completely inhibited by pretreatment with either pargyline or deprenyl. Neither pargyline nor deprenyl had any significant effect on the concentrations of MPTP in brain or heart one-half hr after injection of MPTP into mice. The concentrations of the metabolite, MPP+ (1-methyl-4-phenyl-pyridinium), were markedly reduced in brain and in heart by pretreatment with either pargyline or deprenyl. The data suggest that MPP+ formation, which is necessary for the depletion of brain catecholamines after MPTP injection, may not be necessary for depletion of norepinephrine in heart. Since the oxidation of MPTP in vitro was inhibited more by pargyline or deprenyl pretreatment than was the appearance of MPP+ in vivo , the possibility exists that some MPP+ formation might occur by an enzyme other than MAO.

Increase of catecholamines in mouse brain by systemic administration of gamma-glutamyl L-3,4-dihydroxyphenylalanine.

We investigated the effect of systemic administration of gamma-glutamyl L-3,4-dihydroxyphenylalanine (gamma-Glu-DOPA) on catecholamine contents in the brain. gamma-Glu-DOPA was transformed to dopamine (DA) in vitro with brain homogenate by the sequential action of gamma-glutamyl transpeptidase and aromatic L-amino acid decarboxylase. Intraperitoneal injection of gamma-Glu-DOPA to mice increased DA markedly and noradrenaline (NA) moderately in the brain. The increase of endogenous DA was followed by elevation of the main DA metabolites (3,4-dihydroxyphenyl-acetic acid and homovanillic acid). These increases were in a dose-dependent manner. The maximal elevation of DA was observed within 30 min after administration of gamma-Glu-DOPA, but a substantial increase of NA was observed 2 h after the administration. These results suggest that gamma-Glu-DOPA may be applicable to the treatment of Parkinson's disease.

Effect of Long-Term Exposure to Manganese on Catecholamines in Mouse Brain (Proceedings of the 12 th Symposium on Environmental Pollutants and Toxicology) (Regular Presentations)

Effect of Long-Term Exposure to Manganese on Catecholamines in Mouse Brain (Proceedings of the 12 th Symposium on Environmental Pollutants and Toxicology) (Regular Presentations)

Effect of the saponin fraction ofPanax ginseng on catecholamines in mouse brain

The amount of norepinephrine and dopamine in the brain of the mouse fed with normal diet or protein deficient diet with supplement of the saponin fraction of ginseng were determined by the fluorometric method. The amount of norepinephrine in mouse brain was increased by supplement of the saponin fraction of ginseng throughout the experimental period regardless of the kind of diet. However, the enhancing effect of the saponin fraction of ginseng on the level of norepinephrine in mouse brain was vivider in the case of protein deficiency. The increase amount of dopamine was observed only in the case of mouse fed with normal diet with supplement of the saponin fraction of ginseng for 8 weeks.

Effects of cycloheximide, a protein synthesis inhibitor, on mouse brain catecholamine biochemistry

Cycloheximide (CXM), a protein synthesis inhibitor, has been shown to result in a marked inhibition of central catecholamine (CA) synthetic mechanisms at doses that cause amnesia in animals. Unlike other inhibitors of CA synthesis no significant depletion of whole brain NE or DA concentrations was observed 0.75, 1, 2, 3, 4, 6, 17, or 24 hours after administration of CXM (120 mg/kg) to C57BL/6J mice. In order to investigate the underlying basis of maintenance of CA levels in face of CA synthesis inhibition, the effects of CXM on in vitro release of 3H-NE was studied in mouse hypothalamic slices. CXM, in a dose related manner, significantly inhibited the potassium stimulated release of NE from hypothalamic slices. Anisomycin, another protein synthesis inhibitor, similarly inhibited NE release. These studies further document the effects of protein synthesis inhibitors on CA mechanisms and suggest that disruption of CA biochemistry may play a role in the amnesia observed after administration of protein synthesis inhibitors.

α-methyl-6-aminodopamine: Depletion of catecholamines in mouse brain and peripheral tissues

A new synthetic agent R, S-2-amino-1(2-amino-4, 5-dihydroxyphenyl) propane dihydrobromide, also referred to as α-methyl-6-aminodopamine (α-Me-6-ADA), has been found to produce acute (one day) and longer-term (seven day) depletion of norepinephrine (NE) levels in mouse brain and peripheral tissues. A 100 mg/kg dose of α-Me-6-ADA (i.v., free base) produced greater than 85% depletion of NE in the heart and spleen at one day and one week after treatment. Intracranially, α-Me-6-ADA (100 μg i.vtr.) depleted NE in the telencephalon and brain stem by 79% and 21% respectively at seven days. In addition DA was depleted by 45% in the ipsilateral striatum. The α-Me-6-ADA appears to have a relative selectivity for noradrenergic nerves, as an intracranial dose of 10 μg, which decreased NE in mouse whole brain by 52% at one day, failed to alter the DA content. These data suggest that α-Me-6-ADA may be a neurotoxin.

Effect of piflutixol on turnover of catecholamines in mouse brain and rat corpus striatum.

Dopamine metabolism in vivo was studied after treatment with piflutixol (6-fluoro-9-[3-(4-(2-hydroxyethyl)piperidino)propylidene]-2-trifluoromethyl-thioxanthene) a novel thioxanthene derivative with potent neuroleptic properties and sedative effects. In mice piflutixol increased both noradrenaline (NA) and dopamine (DA) turnover rate measured as increased disappearance of 14C-amines formed from 14C-L-tyrosine. The ratio between the minimal effective doses for 14C-NA and 14C-DA disappearance was 2, which is of the same order of magnitude as obtained with cis(Z)-chlorprothixene, pimozide and chlorpromazine. After 14C-L-tyrosine the accumulation of 14C-dopamine was initially increased after which it decreased from day 4--5. These changes resemble those obtained after other neuroleptics and parallel the initial receptor blockade and the subsequent receptor supersensitivity found in pharmacological experiments (MOLLER NIELSEN et al. 1977). Piflutixol induced a rapid increase in both DOPAC and HVA with a maximal effect after 2--6 hours. After 2--3 days the levels had returned to normal. The doses of piflutixol which at 24 hours doubled the levels of DOPAC and HVA were found to be 0.055 and 0.021 mg/kg subcutaneously, respectively. It is concluded that piflutixol is a powerful and long lasting DA receptor blocking agent, which changes the synthesis and release of DA in a way similar to basic neuroleptics.

Acute and chronic effects of (−)-amphetamine on seizure threshold and brain catecholamines in mice

Acute and chronic effects of (−)-amphetamine on seizure threshold and brain catecholamines in mice

Long-term effects of teflutixol on the synthesis and endogenous levels of mouse brain catecholamines.

Abstract—The long term effects on accumulation of 14C‐labelled dopamine and noradrenaline after [14C]tyrosine administration and on the endogenous levels of catecholamines in mouse brain were studied after treatment with a new potent thioxanthene neuroleptic, teflutixol. The drug was given as a single dose (5 mg/kg i.p.), as repeated daily doses (1·25 mg/kg p.o.), or as a single dose of the palmitic ester in Viscoleo® (20 mg/kg s.c). After a single dose, teflutixol increased catecholamine synthesis (100%). Noradrenaline synthesis rapidly returned to normal, whereas decreased dopamine synthesis was seen from the third to sixth day, after which it was normal. When the receptors were continuously exposed to teflutixol, either by daily dosage or by the depot preparation, catecholamine synthesis was increased for the first few days but then returned to normal, indicating development of tolerance. Endogenous concentrations of catecholamines were only decreased during the first few days, when the increase in synthesis was greatest. The findings are in accordance with results obtained by Møller Nielsen & Christensen (1975), who found that receptor blockade was followed by receptor supersensitivity after treatment with a neuroleptic compound. The receptor blockade may activate a feedback mechanism that induces increased nervous firing with increased amine synthesis as a consequence. The resulting supersensitivity, if sufficiently great, may lead to reduced nervous firing, followed by slowing of dopamine synthesis.

β-Phenylethylamine誘導体の中枢作用(III)Metaraminol脳内投与によるマウスの行動変化

Influence of metaraminol on behavioural changes in mice was studied with the following results. 1) When metaraminol was injected i.c., spontaneous motor activity as tested by either the photocell counters method or open-field test markedly increased within 90 min after injection, while on the contrary greatly decreased 3 hr later as compared with control group. Thus, these biphasic effects of metaraminol were clearly established. 2) 30 min after injection, metaraminol in doses of 160 mug did not alter brain catecholamines in mice, however, 6 hr after injection, brain dopamine and norepinephrine markedly decreased. 3) When metaraminol was injected into mice pretreated with reserpine of 6-hydroxydopamine, spontaneous motor activity tested by photo-cell counters method markedly increased and anti-6-hydroxydopamine activity of metaraminol was stronger than anti-reserpine. 4) Metaraminol completely antagonized ptosis and catalepsy induced by rerserpine. 5) Six hr after injection, anti-methamphetamine activity was observed.

Endogenous levels and turnover of catecholamines in mouse brain after repeated administration of haloperidol.

The endogenous levels of dopamine and noradrenaline in the mouse brain and the accumulation of 14C-labelled catecholamines formed from 14C-tyrosine were investigated in normal and haloperidol pretreated mice. In the withdrawal phase after repeated administration of haloperidol (1.25 mg/kg p. o./day, 5 days) there was an increased synthesis of 14C-dopamine 2 h after the last dose of haloperidol. Synthesis had reverted to normal 24 h later and remained normal for 4 days. The synthesis of 14C-noradrenaline as well as the endogenous level of both dopamine and noradrenaline was unchanged during the 5 days after withdrawal.

Studies on the relationship between the analgesic activity of salicylic acid and the brain catecholamines in mice.

Abstract: The catecholamine content in the mouse brain has been investigated after administration of analgesic doses of salicylic acid. Doses of 300 and 450 mg/kg salicylic acid given orally did not produce any significant changes in brain noradrenaline or dopamine levels in comparison with untreated or placebo treated animals. After inhibition of the rate limiting step of the catecholamine synthesis, salicylic acid in a dose of 300 mg/kg administered orally produced significant acceleration in the decrease of brain noradrenaline induced by the synthesis inhibitor. This acceleration was significantly greater in mice showing analgesic activity and in these animals a significant acceleration was also found in brain dopamine. Furthermore, after inhibition of dopamine β‐hydroxylase with disulfiram, salicylic acid produced a significant reduction of the brain noradrenaline in animals showing analgesic activity. No corresponding changes were found in dopamine concentrations. The results obtained are similar to those obtained with morphine and it seems possible that salicylates may exert a part of their central analgesic action by interference with noradrenergic or dopamin‐ergic neurons. The investigations also showed that the analgesic test procedure used and the manner of injection did not seem to evoke any stress in the animals sufficient to produce changes in the turnover rate of brain noradrenaline or dopamine.

Studies on the relationship between morphine analgesia and the brain catecholamines in mice.

The catecholamine content in the mouse brain has been investigated after the administration of an analgesic dose of morphine. A single dose of 7.5 mg/kg produced a significant reduction in brain noradrenaline during a time‐period of maximal analgesic activity. After inhibition of the rate limiting step of catecholamine synthesis a decrease in noradrenaline content was still obtained. Now even a reduction was found in dopamine content, but this appeared later and was more short‐lasting than the change in noradrenaline. By investigating individual differences in analgesia among animals after inhibition of the catecholamine synthesis or inhibition of dopamine β‐hydroxylation respectively with disulfiram further support was obtained for the view that the release of noradrenaline by morphine is correlated with the analgesic activity better than do changes in dopamine. The possibility that morphine analgesia is induced by interference at the storage sites of brain noradrenaline is discussed.