Effect of barbitone sodium and thiopental sodium on brain dopamine, noradrenaline, serotonin and 5-hydroxyindoleacetic acid content in Arvicanthis niloticus

The quantitative estimation of total dopamine (DA), noradrenaline (NE), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content in the whole brain tissue of normal Nile grass rat, Arvicanthis niloticus, gives and average of 631 +/- 12 ng DA/g, 366 +/- 12 ng NE/g, 617 +/- 15 ng 5-HT/g and 431 +/- 10 ng 5-HIAA/g fresh brain tissue. The effect of barbitone sodium and thiopental sodium on the total DA, NE, 5-HT and 5-HIAA content in the brain tissue of the Nile grass rat, Arvicanthis niloticus, was studied. The total DA, NE, 5-HT and 5-HIAA contents were determined 5 hr after i.p. injection of different doses of barbitone sodium (20, 40 and 80 mg/ml/100 g body wt) and thiopental sodium (5, 10 and 20 mg/ml/100 g body wt). The effect of different time intervals (1, 10, 30 min, 1, 2.5, 5, 8, 16, 24 and 48 hr) on the total brain DA, NE, 5-HT and 5-HIAA content was investigated after i.p. injection of 40 mg of barbitone sodium and 10 mg of thiopental sodium/ml/100 g body wt. Both barbitone sodium and thiopental sodium caused an increase in DA, NE and 5-HT content and a decrease in 5-HIAA content in the brain tissue of Arvicanthis niloticus. The increase in the whole brain contents of DA, NE and 5-HT after the administration of barbitone sodium and thiopental sodium may be due either to inhibition of transmitter release by an action at the monoamine nerve terminal or to effects causing a decrease in nerve impulse flow. On the other hand, the decrease in 5-HIAA may be due to the decrease in the turnover of 5-HT.     

THE EFFECT OF AMINO-OXYACETIC ACID ON BRAIN CATECHOLAMINES

Abstract— —Administration of amino-oxyacetic acid (AOAA) to rats induced a pronounced decrease of midbrain norepinephrine (NE) and adrenal epinephrine (E) after 30 min, at which time the GABA level of midbrain had increased to 117 per cent of the initial value. The concentrations of NE in the pons-medulla and of dopamine (DA) in the cerebral hemispheres were not changed.
Further increases in brain GABA were accompanied by a rise of NE in midbrain and pons-medulla beginning 1 hr after AOAA administration. A rise of cerebral DA level was observed only after 4 hr. Six hours after AOAA administration the levels of both NE and DA in brain were reduced.
From the results of these and other studies, where administration of small amounts of GABA were shown to affect brain NE and serotonin levels, it is suggested that monoamines may be involved in the physiological action of GABA in the brain.     

Impaired noradrenergic transmission in schizophrenia?

Recently, increased brain and spinal fluid (CSF) norepinephrine (NE), and a decreased cAMP response to prostaglandin E₁ (PgE₁) stimulation of platelet NE sensitive adenylcyclase were observed in some schizophrenic patients. Low $\text{CSF}$ dopamine-beta-hydroxylase (DBH) activity was related to brain atrophy, whereas high $\text{plasma}$ DBH was associated with tardive dyskinesia. Increased NE (in brain and CSF) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels and decreased plasma DBH activity in the brain were associated with a diagnosis of paranoid schizophrenia. Impaired NE transmission in schizophrenia may relate to disturbances in the autonomic nervous system, deficits in attention and information processing and to an impaired ability to deal with stress. Although pharmacological studies have suggested a major role for dopamine (DA) in schizophrenic psychosis, this review indicates the need for further exploration of the NE system. Future studies should address the relationship with DA, the autonomic nervous system (ANS), cerebral blood flow, brain metabolism, stress response, negative and prodromal symptoms.     

Central inhibitory effect of Moringa oleifera root extract: possible role of neurotransmitters

Effect of chronic treatment of standardized aqueous extract of Moringa oleifera (MO) root (100, 200, 300, 350, 400, 450 mg/kg; po) on penicillin (PCN) induced convulsion, locomotor behaviour, brain serotonin (5-HTT), dopamine (DA) and norepinephrine (NE) level was studied in Holtzman strain adult albino rats. The result revealed that pretreatment with MO inhibited PCN-induced seizure and markedly reduced locomotor activity. Chronic treatment with MO significantly increased the 5-HT and decreased the DA level in cerebral cortex (CC), midbrain (MB), caudate nucleus (CN) and cerebellum (CB). NE level was significantly decreased in CC but no appreciable change was observed in MB, CB and CN. Thus the central inhibitory effect of MO is discussed in the light of the disturbed balance between 5-HT, DA and NE.     

Effect of chronic administration of phenytoin on regional monoamine levels in rat brain

Phenytoin (DPH) is a widely used anticonvulsant drug but a conclusive mode of action is not yet clear. This study was undertaken to assess the effects of chronic administration of DPH on monoamine levels. DPH (50 mg/kg body weight) was administered to adult male Wistar rats by intraperitoneal injections for 45 days and the regional brain levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were assayed using high performance liquid chromatographic (HPLC) method. The experimental rats revealed no behavioral deficits of any kind nor body and brain weight deficits were observed. Increased NE levels were observed after DPH administration in motor cortex (P<0.05), striatum-accumbens (P<0.01) and hippocampus (P<0.01), whereas, NE level was decreased in brain stem (P<0.05). DA levels were increased in striatum-accumbens (P<0.05), hypothalamus (P<0.001) and cerebellum (P<0.001) but decreased in brainstem (P<0.01). In DPH treated rats, 5-HT levels were increased in motor cortex (P<0.001) but decreased in cerebellum (P<0.001) when compared to control group of rats. The present study suggest that chronic administration of DPH induces alterations in monoamine levels in specific brain regions. DPH seems to mediate, its anticonvulsant action by selectively altering the monoamine levels in different brain regions.     

Effect of cholecystokinin octapeptide sulphate ester on brain monoamines in the rat

The effect of different doses of intracerebro-ventricularly administered cholecystokinin octapeptide sulphate ester (CCK-8-SE) was studied on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents in the hypothalamus, mesencephalon, amygdala, septum and striatum, 10, 20 and 60 min following administration. The DA and NE content increased and the 5-HT content decreased in the hypothalamus and mesencephalon. A biphasic action was observed in the amygdala of DA, NE and 5-HT depending upon the time and doses used. Similar action was seen on DA and NE in the septum. In the striatum, the DA and 5-HT content decreased while the NE level first increased and then decreased. The data indicate that the CCK-8-SE is able to modify the activity of DA, NE and 5-HT in different brain regions in a time and dose-dependent manner, with a local specific action.     

Diurnal alterations of catecholamines, indoleamines and their metabolites in specific brain regions of the mouse

1. The diurnal variations of regional brain concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and metabolites were determined in unperturbed male CD-1 mice. Determinations were made every 4 hr for 24 hr. 2. The most striking and significant variations in biogenic amines were seen in the hypothalamus, where concentrations of NE, DA and 5-HT varied in a rhythmic pattern and as much as two-fold during this period. 3. In some cases, daily alterations in parent biogenic amines were reflected by concurrent changes in their metabolites. 4. Since concentrations of neurotransmitters in the brain are often used as an indicator of stress and/or toxicity, these data should provide an accurate data base allowing for more accurate interpretation of results.     

Effect of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) on monoamine neurotransmitters in mouse brain & heart

The effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was studied on dopamine (DA), norepinephrine (NE), serotonin (5HT) and γ-aminobutyric acid (GABA) neurons in mouse brain and on NE neurons of mouse heart. MPTP (45 mg/kg) was administered s.c. to mice twice daily for 2 consecutive days. This dosage regimen produced a decrease in the forebrain concentrations of DA and NE at 7 and 20 days after injection. In contrast, the forebrain concentrations of 5HT and GABA were not significantly decreased at either time. MPTP administration also produced a marked decrease in the uptake of ³H-DA into striatal slices and ³H-NE into cerebral cortical slices. In contrast, the uptake of ³H-NE into hypothalamic slices and the uptake of ³H-5HT into slices from several brain regions were not altered. MPTP initially reduced the concentration of NE in the heart, but unlike the persistent decreases in the forebrain concentrations of NE and DA, the NE concentration in the heart returned to control levels at approximately 20 days after MPTP administration. These results, showing that MPTP can produce a long lasting and selective decrease in the forebrain concentrations of NE and DA and in the uptake of radioactive DA and NE into brain slices, suggest that MPTP can cause the destruction of catecholamine neurons in mouse brain. In contrast, MPTP administration does not appear to produce long term changes in either 5HT or GABA neurons.     

Alterations in monoamine levels in discrete regions of rat brain after chronic administration of carbamazepine

Carbamazepine (25 mg/kg body weight) was administered intraperitoneally to adult male Wistar rats for 45 days and norepinephrine (NE), dopamine (DA) and serotonin (5-HT) levels were simultaneously assayed in discrete brain regions by high performance liquid chromatographic (HPLC) method. Experimental rats displayed no behavioral abnormalities. Body and brain weights were not significantly different from control group of rats. After exposure it was observed that norepinephrine levels were elevated in motor cortex (P<0.01) and cerebellum (P<0.05), while dopamine levels were decreased in these two regions (P<0.001, P<0.05). However, dopamine levels were increased in hippocampus (P<0.01). Serotonin levels were significantly decreased in motor cortex (P<0.001) and hypothalamus (P<0.001) but increased in striatum-accumbens (P<0.001) and brainstem (P<0.001). These results suggest that carbamazepine may mediate its anticonvulsant effect by differential alterations of monoamine levels in discrete brain regions particularly in motor cortex and cerebellum.     

The effect of phencyclidine on dopamine metabolism in the mouse brain

The administration of phencyclidine (PCP) to mice resulted in no change in brain levels of tyrosine, dopamine (DA), norepinephrine (NE), or homovanillic acid (HVA). Although PCP reduced plasma tyrosine levels, no effect of PCP on the utilization of DA of NE after blockade of synthesis with α-methyl-p-tyrosine (AMPT) was observed. In addition, PCP did not affect the probenecid-induced accumulation of HVA. However, PCP was observed to potentiate the haloperidol-induced increase in HVA concentration, and the haloperidol-induced decline in DA levels after AMPT. The former effect was blocked by baclofen, suggesting that PCP mobilizes DA for impulse-dependent release. This effect could not be attributed to an antagonism of presynaptic DA receptors. These effects are similar to those of the “non-amphetamine” stimulant class of drugs.     

ALTERATIONS IN THE TURNOVER OF BRAIN NOREPINEPHRINE AND DOPAMINE IN ALCOHOL-DEPENDENT RATS

Abstract— The turnover of brain norepinephrine (NE) and dopamine (DA) was studied in five groups of male Sprague-Dawley rats under different conditions of alcohol treatment: no treatment, acute treatment while intoxicated, acute treatment subsequent to elimination of alcohol from the blood, alcohol-dependence while still intoxicated and alcohol-dependence during a withdrawal syndrome. Turnover was determined from the rate of depletion of brain catecholamine levels after inhibition of tyrosine hydroxylase. In rats given a single dose of alcohol, NE turnover was increased, while DA turnover was unaffected during the few first hours after treatment. After that time the turnover of both NE and DA was reduced. In alcohol-dependent rats, whether intoxicated or undergoing a withdrawal syndrome, the turnover of NE was increased, while that of DA was decreased. These data suggest that catecholamines may mediate some of the symptoms of the alcohol withdrawal syndrome in the rat.     

Immortalized dopamine neurons: A model to study neurotoxicity and neuroprotection

6-Hydroxydopamine (6-OHDA) causes selective degeneration of dopaminergic neurons in the rat brain and has been used to produce an animal model of Parkinsonism. Recently, a clonal line of immortalized dopamine (DA) neurons (1RB3AN27), which expresses varying levels of tyrosine hydroxylase, dopamine transporter, neuron specific enolase, and nestin, was established. These DA neurons reduce behavioral deficits in 6-OHDA-lesioned rats. The relative sensitivity of fetal and adult neurons to potential neurotoxins is not well defined. The availability of immortalized DA neurons provides a unique opportunity to compare the relative neurotoxicity of 6-OHDA in differentiated and undifferentiated DA neurons in vitro and identify neuroprotective agents. Our results showed that 6-OHDA treatment for 24 hr decreased the viability of undifferentiated and differentiated immortalized DA neurons in vitro, as determined by the MTT assay, and increased the rate of apoptosis in differentiated DA neurons. The differentiated DA neurons (IC50 = 33 microM) were about 2-fold more sensitive to 6-OHDA than undifferentiated DA neurons (IC50 = 75 microM) in cell culture. Similarly, the differentiated DA neurons were more sensitive to another neurotoxin, 1-methyl-4-phenylpyridinium (MPP+), which is commonly used to induce Parkinsonism in animal models, than were the undifferentiated DA neurons in culture. Among growth factors tested, only glial cell line-derived neurotrophic factor (GDNF) partially protected differentiated DA neurons against 6-OHDA-induced toxicity. These results suggest that undifferentiated and differentiated immortalized DA neurons can be a useful experimental model to study relative sensitivity to neurotoxins and neuroprotective agents that could have relevance to fetal and adult neurons.     

The effect of ascorbic acid on plasma sulfate conjugated catecholamines after eating bananas

The effects of eating bananas, a rich source of biogenic amines, on the plasma concentration of free and sulfate conjugated norepinephrine (NE) and dopamine (DA), and free epinephrine (E), were examined in normal male subjects before and after treatment with ascorbic acid, 2 g daily for 7 days. There were no significant changes in the levels of free NE or E in any subjects after eating a banana, either before or after ascorbic acid. Plasma free DA became detectable in some subjects, but the overall changes were not significant. Sulfate conjugated DA and NE increased markedly after banana ingestion, as previously demonstrated in our laboratory. After ascorbic acid treatment the rise in sulphate conjugated NE was attenuated, presumably because ascorbic acid acts as a competitive inhibitor of sulfate conjugation. In contrast, the rise in conjugated DA was potentiated after ascorbic acid treatment. This may be indicative of the higher affinity of DA for phenolsulfotransferase, an inhibitory effect of ascorbic acid on dopamine-receptor coupling or of ascorbic acid protecting DA from oxidation in the gut.     

Effect of caponization on central nervous system monoamines in the Japanese quail

Depletion of brain regional norepinephrine (NE), dopamine (DA) after alpha methyl-paratyrosine (AMT), and serotonin (5HT) were measured in intact and caponized adult male Japanese quail (Coturnix coturnix japonica). Telencephalon, diencephalon, and cerebellum DA was depleted by AMT treatment, but brain stem was not affected. AMT-induced depletion of NE was greatest in telencephalon, diencephalon, and brain stem of capons. Neither caponization nor AMT affected brain regional 5HT. The results from this work indicate that caponization will affect catecholamine dynamics in brain regions other than the hypothalamus.     

Stability of 3,4-dihydroxyphenylacetic acid in plasma extracts assayed by high-performance liquid chromatography with electrochemical detection

3,4-Dihydroxyphenylacetic acid (DOPAC) can be easily assayed by high-performance liquid chromatography (HPLC) with electrochemical detection at the same time as norepinephrine (NE), epinephrine (E), and dopamine (DA). The latter catecholamines are stable in perchloric acid extracts for over 6 h at 4°C in the dark whereas DOPAC levels drop rapidly by more than 50% in 6 h at 4°C in the dark. This study investigated the effects of reducing agents [ascorbic acid, dithiothreitol (DTT), reduced glutathione with or without a metal chelating agent (diethylenetriaminepentaacetic acid or ethylenediaminetetraacetic acid)] on DOPAC. Extracted with alumina using 0.65 mmol/1 DTT prior to HPLC and electrochemical detection, DOPAC remained stable in the perchloric acid extract for 2 h at 4°C in the dark.     

Influence of hypo- and hyperthyroidism on the turnover rate of noradrenaline, dopamine and serotonin in various rat cerebral structures]

The effect of chronic treatment with tyroxine (T4) or propylthiouracile (PTU) on the turnover of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) has been studied in various areas of the rat brain (brain stem, hypothalamus, striatum and "rest of the brain"). The turnover of NE and DA was determined by the decay in endogenous levels after inhibition of tyrosine hydroxylase by alpha-methylparatyrosine and the turnover of 5-HT was evaluated by the initial accumulation of endogenous 5-HT after inhibition of monoamine oxydase by pargyline. T4 treatment accelerated the release of DA from the striatum but had no significant effects on NA release in the various cerebral areas : nevertheless the NE endogenous level was significantly reduced in the brain stem. PTU treatment delayed the release of DA and NA only from the "rest of the brain". Concerning 5-HT, the only significant variation was observed in the hypothalamus of PTU-treated rats and implied increased turnover. The possible relations between the changes in cerebral monoamines turnover and the behavioural alterations which are observed in thyroid disfunction are discussed.     

Correlation of behavioral and neurochemical effects of acute administration of cocaine in rats.

Effects of cocaine were investigated on spontaneous motor activity (SMA) and stereotypy as well as on the concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and acetylcholine (ACh) in the discrete brain areas, such as the caudate nucleus (CN), diencephalon-midbrain (DM) and pons-medulla (PM) in rats up to 90–120 min following its injection in single doses (15–20 mg/kg, i.p.). After cocaine administration, the SMA was increased usually reaching its peak between 10–20 min, and then decreased gradually. Stereotypy and its components gradually increased to their maximum at about 50–60 min and remained at that level during rest of 120 min sessions. NE levels slightly increased in the DM and PM at 10 min post-drug after which they were decreased at 20 min. DA levels in the CN and DM were increased markedly at 20 min post-drug and decreased at 40 min. 5-HT levels in DM and PM decreased gradually up to 20 min, then began to increase. ACh level in the CN was gradually increased at 40 min and then decreased. It appears that cocaine-induced hyperactivity and stereotypy followed release of NE and DA after their accumulation in the respective brain areas.     

The effect of chronic chlorpromazine administration on monoamine levels in various regions of rat brain

The neuroleptic drug, chlorpromazine (CPZ) has been shown to exert its antipsychotic effect by blocking post synaptic dopamine receptors. However, its effect on steady state levels of monoamines is still in discrepancy. In the present study, CPZ (4 mg/kg body weight) was administered intraperitoneally to adult Wistar rats chronically for 75 days and the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) were assayed in various brain regions by high performance liquid chromatography (HPLC). After the experimental period body and brain weights were not statistically different from controls. NE and 5-HT levels were increased only in hippocampus by 15% (p<0.01) and 16% (p<0.01) respectively. DA levels were consistently increased in cortex by 39% (p<0.001), striatum-accumbens by 18% (p<0.01), hippocampus by 27% (p<0.01), hypothalamus by 34% (p<0.001), cerebellum by 36% (p<0.001) and brainstem by 40% (p<0.001) in CPZ treated rats compared to controls. The results suggest that chronic CPZ administration increases DA levels in almost all regions of brain and reflect the ability of CPZ to preferentially interfere with synaptic transmission mediated by DA in brain. It also suggests that this increase in DA might be responsible for certain side effects seen in patients after chronic CPZ treatment.     

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.     

Circadian variations in plasma growth hormone and prolactin in the infant rat: Comparison with the adult pattern

Radioimmunoassayable (RIA) plasma growth hormone (GH) and prolactin (PRL) levels were determined at 3 hr intervals during a controlled 24-hr light-dark cycle in 10-day-old male and female rats; parallel measurements were made of brain monoamines (MA's), dopamine (DA), norepinephrine (NE) and serotonin (5-HT) concentration. Plasma GH and PRL and brain MA levels found in infant rats were compared to the same determinations made during the 24-hr cycle in 50-day-old male rats. GH levels were rather uniform and did not show circadian periodicity in the plasma of infant rats, while PRL levels showed a diurnal surge in the late afternoon hr (1800). In adult rats, GH levels exhibited wide fluctuations during the 24-hr cycle and no circadian periodicity, while PRL levels showed one diurnal (1500–1800) and one nocturnal (2400) surge. A pulsatile GH secretion was found in adult rats sampled at 15 min intervals over a period of 2 hr, which seemed to be lacking in infant rats. In the brain of infant rats, DA and NE levels exhibited circadian patterns which resembled the ones present in the brain of adult rats, whereas no circadian variations were present in 5-HT levels.