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The effect of amitriptyline and mianserine (Org. GB94) on food motivated behaviour of rats trained in a runway: possible correlation with biogenic amine concentration in the limbic system.

Rats on a 23 h food deprivation schedule were trained to run down a straight runway for a food reward. Neither amitriptyline nor mianserine had an effect on the running time for the food reward during the period of continuous reinforcement. However both antidepressants delayed the extinction of this response. It seems unlikely that this effect on extinction was due to an altered motivation for the food reward as amitriptyline significantly decreased the food intake of the experimental animals while mianserine increased the food intake throughout the period of the experiment. The observation that both these antidepressants reduce the speed of extinction of rewarded behaviour may be explicable in terms of observed changes in the concentration of biogenic amines in the limbic system.

Amitriptyline↗

Withdrawal-like behaviour induced by inhibitors of biogenic amine reuptake in rats treated chronically with delta 9-tetrahydrocannabinol.

The effects of the biogenic amine reuptake inhibitors fluoxetine, clomipramine and imipramine on the behaviour of rats after chronic treatment with delta 9-tetrahydrocannabinol (delta 9-THC) for 5 and 10 days were examined. Rats with permanently in-dwelling IV cannulae were injected twice daily with doses of delta 9-THC (2-6 mg/kg). delta 9-THC treatment reduced the rate of body weight gain and induced the typical biphasic modifications of behaviour. Tolerance developed to both of these effects. On days 6 and 11 of the experiment, rats were injected IP with 15 mg/kg imipramine HCl, clomipramine HCl or fluoxetine HCl, and behaviour, consisting of writhes, backward kicks, jumps and wet shakes, was observed for the next 30 min. Each of the amine reuptake inhibitors induced changes in behaviour, the severity of which appeared to correlate with their ability to inhibit the reuptake of 5-hydroxytryptamine (5-HT). It is suggested that tryptaminergic mechanisms are involved in the production of a withdrawal-like behaviour after chronic delta 9-THC treatment.

Animals↗

Biogenic amines and the effect of short term lithium administration on open field activity in rats.

Experiments were performed to examine whether the effects of short-term lithium administration on cerebral biogenic amine metabolism might be related to its action on open field activity. Rats received intragastric injections of lithium chloride (1.5 mEq/kg) twice daily for 5 days. This lead to a decrease in exploratory behavior in the open field. Administration of imipramine, which blocks the efffects of short-term lithium administration on norepinephrine turnover and uptake in the brain, failed to influence the effect of lithium on exploratory activity. Parachlorophenylalanine, which inhibits cerebral serotonin synthesis and depletes brain catecholamines, prevented the behavioral effect of lithium. Injection of pargyline, which inhibits cerebral monoamine oxidase activity, counteracted the effect of lithium on exploratory behavior and also influenced the emotionality of the animals in the open field. The findings are consistent with the hypothesis that cerebral monoamine levels and monoamine oxidase activity play a role in the effect of short-term lithium administration on open field activity in rats.

Animals↗

Plasma moclobemide and metabolites: lack of correlation with clinical response and biogenic amines.

The concentration of the reversible monoamine oxidase type-A (MAO-A) inhibitor moclobemide (Ro 11-1163) was determined by high pressure liquid chromatography (HPLC) in the plasma of 16 depressives treated with moclobemide. Moreover, the inhibitory potency of organic extracts of the plasma on a standard MAO-A preparation from human placenta was measured spectrophotometrically. The inhibitory potency significantly correlated with the HPLC results. However, it overestimated the concentration of moclobemide by one order of magnitude possibly due to the presence of yet unknown metabolites more active than moclobemide itself. These have already been suggested in view of the higher inhibitory potency of moclobemide ex vivo than in vitro. This new methodological approach might represent a comfortable alternative to HPLC procedures in pharmacokinetic studies on reversible MAO inhibitors. Plasma biogenic amines and their metabolites might be indicative of the biologic activity of moclobemide. Plasma homovanillic acid (HVA) decreased and norepinephrine (NE) increased under moclobemide, although insignificantly. There was no significant correlation between the plasma concentration of moclobemide as estimated by either method and the therapeutic response and the change of plasma HVA and NE.

Adult↗

MPTP lesions of the nigrostriatal dopaminergic projection decrease [3H]1-[1-(2-thienyl)cyclohexyl]piperidine binding to PCP site 2: further evidence that PCP site 2 is associated with the biogenic amine reuptake complex.

Our previous studies have demonstrated that, using membranes of guinea pig brain, [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) labels not only the phencyclidine binding site associated with the NMDA receptor (PCP site 1), but also a second high affinity binding site which is associated with the biogenic amine reuptake carrier (termed PCP site 2). To test this hypothesis, the binding of [3H]GBR12935 to the dopamine transporter, and [3H]TCP binding to PCP sites 1 and 2 were measured in caudates harvested from control, MPTP-treated and reserpine-treated dogs. MPTP treatment decreased dopamine levels by over 99%, decreased [3H]GBR12935 binding by over 90%, decreased [3H]TCP binding to PCP site 2 by about 50%, and had no significant effect on [3H]TCP binding to PCP site 1. These data are consistent with the hypothesis that a portion of PCP site 2 is associated with dopaminergic nerve terminals in dog caudate.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Simultaneous measurement of biogenic amines and their metabolites in rat brain regions after acute administration of and abrupt withdrawal from butorphanol or morphine.

Changes in levels of biogenic amines and metabolites were measured using high performance liquid chromatography fitted with an electrochemical detection in various rat brain regions after acute administration of and abrupt withdrawal from continuous intracerebroventricular infusion of butorphanol (a mu/delta/kappa mixed opioid receptor agonist) or morphine (a mu-opioid receptor agonist). A single dose of butorphanol (26 nmol/5 microliters) or morphine (26 nmol/5 microliters) increased levels of 3,4-dihydroxyphenylacetic acid in the striatum and limbic region and of homovanilic acid in the cortex, striatum, and limbic region. In animals which had been infused with butorphanol (26 nmol/microliters/hr) or morphine (26 nmol/microliters/hr) for 3 days, an increase in dopamine turnover was observed. The levels of 3,4-dihydroxyphenylacetic acid was decreased and that of homovanilic acid was increased in the striatum, limbic region, and midbrain immediately after termination of opioid infusion. Both dopamine metabolites (in these areas) were decreased at 2 and 6 hr after butorphanol or morphine withdrawal. Changes in norepinephrine, serotonin, and 5-hydroxyindoleacetic acid levels in some brain regions were observed in the morphine-, but not in butorphanol-dependent rats. These data suggest that the increase and the decrease in dopaminergic activity, but not noradrenergic and serotonergic neurons, in the some brain regions are closely associated with the production of antinociception of and the expression of withdrawal syndrome from butorphanol and morphine, respectively.

Animals↗

Microspectrofluorometric characterization of the fluorescent derivatives of biogenic amines produced by aqueous aldehyde (Faglu) fixation.

The fluorescent derivatives of the reaction between an aqueous aldehyde (Faglu) solution and the biogenic amines (5-hydroxytryptamine, dopamine and noradrenaline) have been examined in the order to determine the conditions required for maximal fluorescence yield. The fluorescence intensity and spectra of the final reaction products have been characterized and found to be highly dependent on the pH of the reaction mixture, Fluorophores derived from catecholamines have maximal yield and are most easily characterized when the reaction is performed at pH 7.3, whilst those derived from 5-hydroxytryptamine have maximal yield and are most readily characterized when the reaction is performed at pH 10.0. The addition of potassium ferricyanide to the Faglu further enhances the fluorescence yield of 5-hydroxytryptamine-containing models and tissues at both pH 10.0 and pH 7.3. Using the modified Faglu reaction mixture, it has been possible to demonstrate 5-hydroxytryptamine in the central nervous system without the need for pharmacological manipulation.

Animals↗

[Determination of biogenic amines by RP-HPLC for monitoring the microbial spoilage of poultry].

A simple high-performance liquid chromatographic (HPLC) analysis is described for the determination of biogenic amines in broiler carcasses. The clean-up procedure consists of an extraction with 0.6 M-perchloric acid, formation of dansyl derivatives, separation by a RP-18 column and UV detection at 254 nm. Within 7 min eight amines could be separated. The quantitative determination of spermidine and spermine requires an additional ion-exchange clean-up with Amberlite CG 50 after the extraction. This procedure gives recoveries of 82%-96% with detection limits of 0.2-0.5 microgram/g of broiler skin. Putrescine and cadaverine are good indicators for the onset of spoilage of poultry carcasses, since both amines could be detected at total colony counts of 10(5) cfu/cm2 and their concentration increases rapidly with advancing decomposition.

Animals↗

Formation of biogenic amines in herring and mackerel.

The formation of biogenic amines (histamine, cadaverine, putrescine and spermidine) was followed during vacuum packed storage at 2 degrees C or 10 degrees C in the scombroid fish mackerel and in the non-scombroid fish herring. Also the changes in the content of free amino acids and in the organoleptic and microbiological qualities were followed. At 10 degrees C the amine contents were 2-20 times higher at the time of rejection as compared with samples stored at 2 degrees C. In herring and mackerel similar amounts of histamine were accumulated, whilst cadaverine was formed at much higher levels in mackerel compared with herring. The high contents of cadaverine in mackerel can possibly explain why mackerel and not herring are often implicated in incidents of scombrotoxic poisoning.

Amino Acids↗

Change in the activity of cortical neurons under the influence of biogenic amines.

Under the conditions of extracellular recording of action potentials, the influence of proposed neuromediators on the structure of background impulse activity of neurons of various regions of the cerebral cortex was studied. Computer analysis of the statistical parameters of impulse flows revealed the presence of a fundamental difference between the effects of neuromediators of cortical and subcortical origin. It was demonstrated that prolonged application of serotonin and noradrenalin evokes a change in structure of cortical neuron impulse activity more complex than the simple inhibition and excitation characteristic of acetylcholine or GABA. Different types were found of the reaction of neurons to the same monoaminergic stimulus, types whose characteristic feature is the dependence of the end result of the influence on the initial level of excitation in the neuron examined. The fundamental difference between the effects of preparations studied in the visual and sensorimotor regions of the cortex was not discovered. The data obtained are considered from the point of view of the modulating role of the biogenic amines in the regulation of the level of excitation of cerebral cortical neurons.

Acetylcholine↗

Extraction and determination of biogenic amines in fermented sausages and other meat products using reversed-phase-HPLC.

A convenient method is described for the analysis of biogenic amines (BA) by means of reversed-phase-HPLC. The method is characterized by multi-channel UV detection (diodearray), subsequent post-column derivatization with o-phthaldialdehyde and 3-mercaptopropionic acid, and fluorescence detection. For the analysis of meat products and especially fermented sausages an optimized perchloric acid extraction process was introduced to determine putrescine, cadaverine, histamine, tyramine and 2-phenylethylamine. BA recoveries from meat ranged between 96 and 113% with a detection limit for amines of 0.5 mg/kg.

Amino Acids↗

Determination of biogenic amines in leafy vegetables by amino acid analyser.

An automated ion-exchange chromatographic method is described for determination of biogenic amines in leafy vegetables using a cation-exchange resin column in potassium form and a three-buffer system. The following amines were separated and quantified for Chinese cabbage, endive, iceberg lettuce and radiocchio: putrescine, histamine, cadaverine, spermidine, agmatine, spermine, tyramine. Amines from vegetable samples were extracted with 10% trichloroacetic acid. The total concentration of these amines ranged from 14 to 20 micrograms/g fresh weight. Spermidine was the major polyamine detected, present at concentrations of 7-15 micrograms/g fresh weight.

Biogenic Amines↗

The formation of biogenic amines by fermentation organisms.

A total of 523 strains representing 35 species related to food fermentation organisms of practical importance were investigated for their potential for formation of biogenic amines (BA). The investigation was performed with resting cells in phosphate buffer (pH 5.5) and the formation of the following BAs was followed: putrescine, cadaverine, histamine, tyramine and 2-phenylethylamine. No potential was observed in species of lactococcus, Leuconostoc, Pediococcus, Streptococcus and several Lactobacillus spp., such as L. Pentosus and L. sake. A remarkable potential to form BA was observed in strains of carnobacteria, Lactobacillus buchneri, L. curvatus, L. reuteri, Staphylococcus carnosus and, to a lesser extent, in L. alimentarius, L. brevis, L. bavaricus, L. delbrueckii ssp. lactis, Micrococcus spp. and S. piscifermentans. In well known species with a practical function in the fermentation of dairy products, wine or cabbage a potential was observed for few strains only. In view of their role as starters in food fermentation, or their potential use in protective cultures and as probiotics, BA formation by the organisms has to be taken into consideration by selecting appropriate strains.

Bacteria↗

Inhibitory effect of spices on in vitro histamine production and histidine decarboxylase activity of Morganella morganii and on the biogenic amine formation in mackerel stored at 30 degrees C.

The inhibitory effects of clove, cinnamon, cardamom, turmeric and pepper on the histamine production and histidine decarboxylase activity of Morganella morganii (a potent histamine-producing bacteria in fish) was examined at 30 degrees C using HPLC. Cinnamon and clove exhibited a significant (P < 0.01) inhibitory effect, whereas turmeric and cardamom had a moderate effect. These spices were applied to whole mackerel at a level of 3% and their inhibitory effect on biogenic amine formation at 30 degrees C was also examined. As in the in vitro study, clove and cinnamon showed a significant (P < 0.05) inhibitory effect on histamine, putrescine and tyramine formation but not on that of cadaverine. Cardamom and turmeric exhibited a moderate effect and pepper was ineffective. Therefore, clove and cinnamon are more helpful than cardamom and turmeric in the minimization of the formation of toxic histamine in mackerel.

Analysis of Variance↗

Influence of active immunization of rats with conjugated serotonin-protein antigen on the content of biogenic amines in the brain and on behavioral responses.

The influence of induction of antibodies to the neuromediator serotonin in the case of active immunization of animals with a conjugate serotonin-protein antigen on the distribution of biogenic amines in the brain and on behavioral responses was investigated in experiments on rats. It was shown that active immunization of rats with a serotonin-protein conjugate leads to a decrease in serotonin, its metabolite 5-hydroxyindole-3-acetic acid, as well as dopamine in certain brain structures. Against a background of induction of antibodies to serotonin, the horizontal motor activity of the animals is decreased.

Animals↗

[New possibilities for demonstration of some biogenous amines in the adrenal by X-ray microanalysis (author's transl)].

Technical possibilities for the histochemical demonstration of some biogenous amines with the scanning electron-microscope and X-ray microanalysis were shown by using argentaffine and chromaffine reactions. Objects were adrenals of adult minipigs. Beside morphologic studies the amounts of silver or chromium can be determined semiquantitatively by the intensity of the specific X-radiate from "sum up-analysis" out of punctual areas. Furthermore the high amine concentrations in the adrenal medulla permit the performance of "line-analysis" and of "element-distribution-pictures" for silver or chromium. At the points chosen for analysis the concentration of epinephrine + norepinephrine is six times as high in the adrenal medulla as in the cortex; for norepinephrine alone it is only three times higher. Line-analysis shows that the concentration of katecholamines in the cortex is very low in the periphery and high near the medulla. The chromaffine reaction for serotonin leads to a distinct chromium peak in the medulla with a distribution quotient of 4.6 : 1 versus the cortex showing that there must be remarkable amounts of serotonin in the adrenal medulla, inspite of the fact that serotonin cannot by synthetized there from its natural precursor.

Adrenal Cortex↗

Biogenic amines and metabolites in spinal cord of patients with Parkinson's disease and amyotrophic lateral sclerosis.

In four human controls, four cases of Parkinson's disease and three cases of amyotrophic lateral sclerosis analysis of dopamine, noradrenaline, serotonin and the metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid was performed in various segments of postmortem spinal cord. In controls the concentrations of dopamine are about 1/3 to 1/4 that of noradrenaline; the significantly highest content of noradrenaline was found in the lumbar, and dopamine in thoracic, lumbar and sacral segments of the spinal cord. Intersegmental distribution of monoamines was only present in spinal cord of controls, while in the spinal cord of parkinsonian patients such a difference was not found. Otherwise, biogenic amine and metabolite concentrations in spinal cord segments of parkinsonian patients did not differ significantly from those in the control subjects. However, it cannot be excluded that these segments are sensitive to drugs including neuroleptics and combined L-DOPA treatment. In subjects with amyotrophic lateral sclerosis significantly lower concentrations of noradrenaline in the cervical and thoracic, and of dopamine and homovanillic acid in the thoracic and lumbar segments were found in comparison with controls. The concentrations of serotonin and 5-hydroxyindoleacetic acid in the thoracic segments of amyotrophic lateral sclerosis were significantly lower than that of controls. Differences in the inter-segmental distribution of noradrenaline in lumbar, lumbar-sacral, and serotonin in lumbar segments of spinal cord were found in this group.

3,4-Dihydroxyphenylacetic Acid↗