Showing papers in "Journal of Neural Transmission in 1986"
TL;DR: The histological findings in the two limbic regions consisted mainly of poorly developed structure in the upper layers, with a heterotopic displacement of single groups of nerve cells in the entorhinal region, which suggests a disturbance of neuronal migration in a later phase of cortical development.
Abstract: Sixty-four autopsied brains of schizophrenic patients were neuropathologically examined and compared with 10 brains of non-schizophrenic controls. Clinical diagnoses were established retrospectively according to the Research Diagnostic Criteria and the International Classification of Diseases. We found:
Generally, these anatomical abnormalities were asymmetric. The histological findings in the two limbic regions consisted mainly of poorly developed structure in the upper layers, with a heterotopic displacement of single groups of nerve cells in the entorhinal region. Particularly, the disturbed structure of the second layer Pre-α in medial and central fields of the entorhinal region, situated in the parahippocampal gyrus (group 2 a), suggests a disturbance of neuronal migration in a later phase of cortical development.
833 citations
TL;DR: The tritium (3H) release was investigated during potassium stimulation, and AD/SDAT cortical slices were found to release a decreased amount of3H compared to control brain slices.
Abstract: A technique was developed, which made it possible to study the in vitro release of 3H-acetylcholine (3H-ACh) from human post mortem brain tissue, collected with short post-mortem delay (2,5-22 hours), both from controls and patients with Alzheimer's disease (AD/SDAT). The tritium (3H) release was investigated during potassium stimulation, and AD/SDAT cortical slices were found to release a decreased amount of 3H compared to control brain slices. Physostigmine, 10(-5) and 10(-4) M, has no significant effect on the release of 3H from control slices, while physostigmine 10(-4) M increased the evoked release from AD/SDAT brain slices over threefold, nearly to the control level.
121 citations
TL;DR: A series of 203 patients with primary Parkinson's disease treated with L-DOPA, with adequate neurological documentation of mental status at serial intervals during their illness, constitutes the study population.
Abstract: A series of 203 patients with primary Parkinson's disease treated with L-DOPA, with adequate neurological documentation of mental status at serial intervals during their illness, constitutes the study population. Based on the results of the latest neurological examination, slightly less than one-third (29%) had mental impairment assessed as neurologically significant. Of the eleven clinical variables analysed (Cox regression analysis) for potential influence on the occurrence of an organic mental syndrome, four had a statistically significant effect: (1) the stage of disease at initial neurological examination; (2) the occurrence of acute confusional states; (3) the years of Parkinson's prior to L-DOPA; and (4) the total duration of L-DOPA therapy. The pathogenesis of dementia in this subgroup of Parkinson's disease is discussed.
104 citations
TL;DR: Evidence of the inhibitory effect of melatonin on beta-endorphin secretion and the stimulatory action of the opioid peptides on the pineal gland is provided, however, further studies will be required to clarify the relationship between the opioid system and the Pineal gland.
Abstract: Recent reports point to a link between the pineal gland and the opioid system. In order to investigate this relationship, two separate studies were performed on humans. Beta-endorphin plasma levels were determined after melatonin administration (0.2 mg/kg b.w. i.m. at 2 p.m.). Melatonin serum values were evaluated after administration of FK 33-824, a met-enkephalin analogue (0.3 mg i.v. infusion at 9 a.m.). A significant decrease of beta-endorphin plasma levels was observed 120 minutes after melatonin injection. Melatonin release was stimulated by FK 33-824, with a peak at 30 minutes. The present results provide evidence of the inhibitory effect of melatonin on beta-endorphin secretion and the stimulatory action of the opioid peptides on the pineal gland. However, further studies will be required to clarify the relationship between the opioid system and the pineal gland.
97 citations
TL;DR: The results tend to support the proposal that the H 1-receptor intervenes in sleep-wakefulness regulation, and to suggest that two different mechanisms could be involved in the 2-TEA-induced effects on NREMS and REMS.
Abstract: The H 1-receptor agonist 2-thiazolylethylamine (2-TEA) given by i.c.v. route dose-dependently increased wakefulness (W) and decreased NREM sleep (NRMS) and REM sleep (REMS) in rats prepared for chronic sleep recordings. The H 1-receptor antagonists pyrilamine and diphenhydramine given by i.p. route decreased W and increased NREMS. Pyrilamine prevented the increase of W and decrease of NREMS produced by 2-TEA. However, REMS reduction was not antagonized, what tends to suggest that two different mechanisms could be involved in the 2-TEA-induced effects on NREMS and REMS. Cimetidine which blocks H 2-receptors, when given by i.p. route showed no significant effects on sleep and W. Administration of the H 2-receptor agonist dimaprit and the H 2-receptor antagonists cimetidine, metiamide and ramtidine by i.c.v. route induced the appearance of high voltage spikes at cortical leads, thus leaving inconclusive the matter of their effects on sleep and wakefulness. Our results tend to support the proposal that the H 1-receptor intervenes in sleep-wakefulness regulation. Limitations in the available H 2-receptor agonists and antagonists presently preclude a more detailed analysis of the role of H 2-receptors on sleep and W.
97 citations
TL;DR: In a double-blind placebo-controlled cross-over study the encephalotropic and psychotropic properties of sertraline were studied along with blood levels of the parent drug and main metabolite in ten normal healthy volunteers, supporting neurophysiological conclusion that vigilance changes of the dissociative type are reflected.
Abstract: In a double-blind placebo-controlled cross-over study the encephalotropic and psychotropic properties of sertraline--a new potent and highly selective inhibitor of synaptosomal serotonin uptake--were studied along with blood levels of the parent drug and main metabolite in ten normal healthy volunteers They received randomized at weekly intervals oral single doses of placebo, 100, 200 and 400 mg setraline and 100 mg zimelidine as reference drug Blood sampling, EEG recordings, psychometric tests and evaluation of pulse, blood pressure and side-effects were carried out at the hours 0, 2, 4, 6, and 8 Blood level investigations demonstrated that sertraline is slowly absorbed with dose-dependent blood concentrations peaking in the 4th to 6th hour and remaining high thereafter, while the main metabolite, CP-53261 exhibited an even slower rise in plasma concentration up to the 8th hour Computer-assisted spectral analysis of the EEG demonstrated slight effects of 100 mg zimelidine and 100 mg sertraline on human brain function, but moderate to marked effects after 200 and 400 mg sertraline as compared with placebo Changes after 100 mg sertraline and the reference compound resembled the pharmaco-EEG profiles of antidepressants of the desipramine type and were indicative of some vigilance-improving properties while higher doses of sertraline induced alterations reminiscent of those after antidepressants of the imipramine type, thereby reflecting vigilance changes of the dissociative type This neurophysiological conclusion was supported by the psychometric and psychophysiological data showing partly after 100 mg sertraline and zimelidine an improvement in psychometric performance, while 200 and 400 mg sertraline induced a deterioration of noopsyche and thymopsyche of the normal volunteers Psychophysiological variables exhibited a dose-dependent change in CNS activation and a widening of the pupillary size Time-efficacy calculations based on pharmacodynamic changes demonstrated maximal encephalotropic effects after 100 mg zimelidine in the 2nd to 4th hour, and after setraline in the 4th to the 6th hour, which is in agreement with the blood level data Pulse, systolic and diastolic blood pressure showed no clinically relevant findings Side-effects were non-existent to minimal after 100 mg zimelidine and sertraline, but marked after 200 and 400 mg sertraline characterized by nausea, vomiting, diarrhea, giddiness, restlessness, tremor and trismus
72 citations
TL;DR: Results indicate that Mel administration and/or underfeeding during the promotional phase inhibit DMBA-induced mammary tumorigenesis perhaps via neuroendocrine and/ or peripheral endocrine mechanisms.
Abstract: The effects of melatonin (Mel) and/or underfeeding (30% food restriction) on 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumorigenesis were examined in female Sprague-Dawley rats fed a semipurified diet. During the promotional phase of tumorigenesis, the animals began receiving either daily afternoon Mel (250μg) or saline vehicle injections s.c. for 15 weeks. As compared with fed animals, underfed rats had a lower tumor incidence, tumor number and size while the latency to onset and regression of tumors was increased. Melatonin in fed rats moderately suppressed tumor incidence and number. However, the combination of Mel treatment and underfeeding caused the most marked inhibition of tumorigenesis as compared with either treatment alone. These results indicate that Mel administration and/or underfeeding during the promotional phase inhibit DMBA-induced mammary tumorigenesis perhaps via neuroendocrine and/or peripheral endocrine mechanisms.
64 citations
TL;DR: It is suggested that the nicotine component of the cigarette smoke via activation of nicotinic cholinergic receptors can enhance DA release in discrete DA nerve terminal systems of the nucleus accumbens and tuberculum olfactorium.
Abstract: By means of a Walton smoke machine male rats were exposed to cigarette smoke from 1 to 4 cigarettes. Dopamine (DA) levels and utilization in the telencephalon were measured by quantitative histofluorimetry in discrete DA nerve terminal systems of the neostriatum, nucleus accumbens and tuberculum olfactorium. Exposure to unfiltered but not to filtered (Cambridge glass fibre filter) cigarette smoke resulted in a dose-dependent increase in DA utilization in the diffuse types of DA nerve terminal systems in the anterior nucleus accumbens and the lateral posterior tuberculum olfactorium. After exposure to the smoke from 4 cigarettes also an increase in DA utilization was observed in the dotted type (also cholecystokinin [CCK] positive) of DA nerve terminals of the nucleus accumbens (posterior part). The DA utilization in various parts of the neostriatum and in the dotted type of DA nerve terminals in the medial posterior tuberculum olfactorium were unaffected by acute intermittent exposure to cigarette smoke. The DA levels in the various DA nerve terminal systems in neostriatum, nucleus accumbens and tuberculum olfactorium were unaffected with the exception of the dotted and CCK positive type of DA nerve terminals of the nucleus accumbens, where a small reduction of the DA stores was shown following acute intermittent exposure to smoke from 4 cigarettes. The effects induced by exposure to the cigarette smoke in the limbic DA terminals were counteracted by mecamylamine pretreatment. It is suggested that the nicotine component of the cigarette smoke via activation of nicotinic cholinergic receptors can enhance DA release in discrete DA nerve terminal systems of the nucleus accumbens and tuberculum olfactorium. These actions may at least in part mediate the euphoria induced by inhalation of cigarette smoke.
51 citations
TL;DR: The results support the notion that platelet MAO is a biological marker for some trait dependent property of the central serotonergic system.
Abstract: Platelet monoamine oxidase (MAO) activity and concentrations of 5-HIAA and HVA in the cerebrospinal fluid (CSF) were estimated in a series of 54 chronic pain patients. Platelet MAO activity was found to correlate, positively to CSF concentrations of 5-HIAA and HVA, which had been adjusted in order to eliminate the influence of age and body height. However, only the correlation with 5-HIAA reached a significant level. When partial correlations were sought, only the positive correlation between platelet MAO activity and CSF 5-HIAA remained. The results support the notion that platelet MAO ia a biological marker for some trait dependent property of the central serotonergic system.
49 citations
TL;DR: Nimodipine appears to reduce the release as well as the synthesis of DA in mouse brain and is believed to be related to the Ca2+-antagonism of nimmodipine.
Abstract: The effects of the Ca2+-antagonist nimodipine on central dopamine (DA) neurons in mice were investigatedin vivo. Nimodipine caused a dose-dependent decrease in the DA metabolite 3-methoxytyramine (3-MT) in striatum and the limbic region. If the brains were microwave radiated immediately after decapitation in order to minimize post-mortal accumulation of 3-MT, the effect of nimodipine was less pronounced and statistically not significant. Nimodipine markedly decreased the accumulation of 3-MT induced by pargyline, an inhibitor of monoamine oxidase, a phenomenon that was not attenuated by microwave radiation. Furthermore, whereas nimodipine had no effect on mouse motor activity when given alone it readily blocked the pargyline-induced increase in activity. The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in striatum and the limbic region were also reduced by nimodipine as was the accumulation of 3,4-dihydroxyphenylalanine (DOPA) measured after inhibition of the aromatic amino acid decarboxylase by 3-hydroxybenzylhydrazine (NSD 1015). In addition, nimodipine caused decreased concentrations of DA and homovanillic acid (HVA) in the limbic region but not in striatum. Nimodipine caused an increase in the striatal concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA); these changes were not seen in the limbic region. In conclusion, nimodipine appears to reduce the release as well as the synthesis of DA in mouse brain. These effects are believed to be related to the Ca2+-antagonism of nimodipine.
46 citations
TL;DR: It is shown that Protein-rich meals, when consumed in the morning after an overnight fast, have been shown to decrease the plasma tryptophan ratio, while carbohydrate- rich meals have the opposite effect, and these meals have similar effects when consumed for lunch, even if they are preceded by a small breakfast meal.
Abstract: It is well established that the ratio of the plasma tryptophan concentration to those of the other large neutral amino acids determines the transport of tryptophan into the brain. Brain tryptophan levels, in turn, control production of the neurotransmitter serotonin. Protein-rich meals, when consumed in the morning after an overnight fast, have been shown to decrease the plasma tryptophan ratio, while carbohydrate-rich meals have the opposite effect. We now show that these meals have similar effects when consumed for lunch, even if they are preceded by a small breakfast meal.
TL;DR: The (+)- and (−)-enantiomers of the 2-aminotetralin derivatives cis-5-methoxy-1-methyl-2-(di-n-propylamino)tetralins may prove useful as experimental tools and as potential therapeutic agents (selectively increasing DA-ergic neurotransmission),e.g. in geriatric practice.
Abstract: The (+)- and (-)-enantiomers of the 2-aminotetralin derivatives cis-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin (UH 232) and cis-5-hydroxy-1-methyl-2-(di-n-propylamino)tetralin (UH 242), were pharmacologically evaluated in rats in an extensive series of in vivo biochemical and behavioral experiments. These studies showed that the (+)- and (-)-enantiomers have differential effects on central dopamine (DA) receptors. Thus, (-)-UH 242 is a DA-receptor agonist stimulating both pre- and postsynaptic receptors. (-)-UH 232 is also active as a DA receptor agonist, although with much lower potency than (-)-UH 242. In contrast, (+)-UH 242 and (+)-UH 232 are characterized as DA receptor antagonists. Both (+) forms markedly accelerated DA synthesis and turnover and reversed the biochemical and behavioral effects of apomorphine. Locomotor activity was stimulated by the (+)-enantiomers over a wide dose range; hypomotility was induced only by high doses. The pharmacological profile of the (+)-enantiomers clearly differs from that of classical neuroleptics and suggests a preferential antagonistic action on DA autoreceptors. (+)-UH 232 and (+)-UH 242 may prove useful as experimental tools and as potential therapeutic agents (selectively increasing DA-ergic neurotransmission), e.g. in geriatric practice.
TL;DR: It is suggested that the increase in MAO B activity in the caudate nucleus may reflect neurochemical changes that are responsible for the choreiform movements of Huntington's disease.
Abstract: Activity (Vmax) of monoamine oxidase (MAO) B in necropsy samples from the head of the caudate nucleus was 260% higher in patients dying with Huntington's disease (HD) than in controls (P less than 0.05). No differences in MAO A enzyme kinetics were found. MAO B, but not MAO A, was increased (26%) in the frontal cortex from patients dying with HD compared to control subjects. MAO A and B kinetics in caudate nucleus and frontal cortex from a group of schizophrenics did not differ from controls. Postmortem delay, the effect of neuroleptics, or nonspecific degeneration artifacts did not explain these findings. It is suggested that the increase in MAO B activity in the caudate nucleus may reflect neurochemical changes that are responsible for the choreiform movements of Huntington's disease. Lower cortical MAO B activity in the schizophrenic group may reflect the effects of neuroleptics.
TL;DR: It is concluded that these two behavioural models are selectivein vivo measures of relative D-1 and D-2 receptor activity of DA antagonists.
Abstract: The effects of 30 dopamine (DA) antagonists, including 4 as stereoisomeric pairs, on circling behaviour induced by the D-1 agonist SKF 38393 and the D-2 agonist pergolide in rats with unilateral 6-hydroxy-DA lesions have been studied. SKF 38393-induced circling was selectively blocked by the specific D-1 antagonists SCH 23390 and SKF 83566, and was furthermore blocked by other DA antagonists with potencies correlating to their affinities to D-1 receptors labelled by 3H-SCH 23390 in vitro. Pergolide-antagonistic potencies in contrast correlated to affinities to D-2 receptors labelled by 3H-spiperone in vitro. Pergolide-induced circling was selectively blocked by the specific D-2 antagonists in the benzamide series. No interaction between D-1 and D-2 antagonists was observed in combination experiments with SCH 23390 and YM 09151-2 in both circling models. Among other reference neurotransmitter antagonists acting on alpha- and beta-adrenoceptors, histamine, serotonin and muscarinic receptors, only the alpha 1-adrenoceptor antagonist prazosin was effective in high doses. In contrast, the alpha 2- and beta-adrenoceptor agonists clonidine and clenbuterol as well as the muscarinic agonist RS 86 inhibited circling induced by SKF 38393 as well as pergolide. The 5-HT1A agonist 8-OHDPAT inhibited pergolide-induced circling only. It is concluded that these two behavioural models are selective in vivo measures of relative D-1 and D-2 receptor activity of DA antagonists.
TL;DR: The findings of this study on dopamine D-2 receptors suggest the involvement of the nigrostriatal dopaminergic system in AD but not in the other two major types of dementia.
Abstract: Brain dopamine D-2 receptors were analysed in the caudate nucleus, putamen and nucleus accumbens in 49 patients with different types of neuropathologically verified dementia and in 39 controls by the binding of3H-spiroperidol. The binding was significantly decreased in all brain areas in patients with Alzheimer's disease (AD), while the changes in patients with multi-infarct dementia (MID) or combined dementia (CD) were non-significant. According to a Scatchard analysis, this decrease in binding was due to the reduced number of receptors. On the other hand, the binding of3H-spiroperidol was significantly increased in those patients who had received neuroleptic drugs. Significant correlations between3H-spiroperidol binding and neuropathological changes were seen only in AD patients in the nucleus accumbens. The nucleus accumbens was also the only brain area in which there was a significant correlation between dopamine D-2 and the number of muscarinic receptors in AD patients. The findings of this study on dopamine D-2 receptors suggest the involvement of the nigrostriatal dopaminergic system in AD but not in the other two major types of dementia.
TL;DR: Using ultra-filtration steps and HPLC-separation, a low molecular weight ligand of the benzodiazepine receptor was isolated from plasma of various mammalian species including man and apparently has a receptor affinity similar to Diazepam.
Abstract: Using ultra-filtration steps and HPLC-separation, a low molecular weight ligand of the benzodiazepine receptor was isolated from plasma of various mammalian species including man. The endogenous ligand acts on benzodiazepine receptors agonistically and apparently has a receptor affinity similar to Diazepam. The ligand is not identical with Diazepam as indicated by HPLC and UV-spectroscopy.
TL;DR: The administration of estrogen to ovariectomized rats will result in a dopamine receptor hyposensitive phase at 24 hours followed within 48 hours by a hypersensitive phase, which is characterized by a significant decrease in the ratio of high/low agonist affinity states of the striatal D-2 receptor.
Abstract: The administration of estrogen to ovariectomized rats will result in a dopamine receptor hyposensitive phase at 24 hours followed within 48 hours by a hypersensitive phase In an attempt to characterize further the molecular mechanism(s) which underlie this biphasic response, we studied the effects of estrogen and one of its metabolites (2-hydroxyestradiol) on striatal D-2 dopamine receptor agonist affinity states
TL;DR: In studies on superfused synaptosomes from the rat medulla oblongata, the inhibitory effects of theα2-adrenergic agonist clonidine induced3H-noradrenaline (NA) release was potentiated by 20%, when neuropeptide Y was added to the system.
Abstract: In studies on superfused synaptosomes from the rat medulla oblongata, the inhibitory effects of theα2-adrenergic agonist clonidine (0.1μM) on potassium (15 mM K+) induced3H-noradrenaline (NA) release was potentiated by 20%, when neuropeptide Y was added to the system. The effect of NPY was detectable at low concentrations (1 nM) and was not dose-dependent. Neuropeptide Y alone produced no significant effects on3H-NA release. The results may indicate the existence of a presynaptic NPY receptor on the noradrenaline and/or adrenaline nerve terminals, which may enhance the presynapticα2-adrenoreceptor function to inhibit3H-NA release.
TL;DR: Using tissue taken post mortem from patients with neuropathologically confirmed Huntington's disease and a series of appropriate control cases, GABA, dopamine and homovanillic acid were measured in the caudate nucleus and the putamen and the previously reported loss of GABA was confirmed.
Abstract: Using tissue taken post mortem from patients with neuropathologically confirmed Huntington's disease and a series of appropriate control cases, GABA, dopamine and homovanillic acid were measured in the caudate nucleus and the putamen. The previously reported loss of GABA in Huntington's disease was confirmed, while no change in dopamine concentrations and a loss of homovanillic acid in these striatal regions were observed. This loss could not be explained on the basis of agonal state or previous drug treatment.
TL;DR: A low molecular weight fraction of human urine which both inhibits monoamine oxidase and benzodiazepine binding to central and peripheral receptors has been purified by ethyl acetate extractions, HPLC and thin layer chromatography.
Abstract: A low molecular weight fraction of human urine (less than 500 daltons) which both inhibits monoamine oxidase and benzodiazepine binding to central and peripheral receptors has been purified by ethyl acetate extractions, HPLC and thin layer chromatography. This material extracted equally well at acid and basic pH and was insoluble in heptane. It competitively inhibited binding of 3H-clonazepam, a central benzodiazepine receptor agonist and, in addition, displaced 3H-Ro 5-4864, a specific peripheral benzodiazepine receptor ligand, from its binding sites. It showed no GABA shift with the benzodiazepine receptor antagonist, Ro-15 1788. MAO A and B were inhibited approximately equipotently and the material competitively inhibited tyramine oxidation by rat liver. It was stable on boiling and is unlikely to be a peptide.
TL;DR: It is suggested that CDP-choline enhances norepinephrine release, and that this action may be mediated by more than just its choline content.
Abstract: We examined the effects of orally administered cytidine(5′)-diphosphocholine (CDP-choline) on the total levels of 3-methoxy-4-hydroxyphenyl-glycol (MHPG) in human and rat urine. Four subjects who had been on a low-choline diet (less than 1 gm/day) for 24 hours received three doses of CDP-choline (2 gm each) at 8 a.m., 10 a.m., and noon; urines were collected at two-hour intervals after each dose. Rats received water for three days; then CDP-choline (100 mg/kg) or equimolar doses of choline for five days; then water again for three more days. Twenty-four hour urine samples were collected on each day of the study. The levels of MHPG in human urine increased by 45–68% when subjects were receiving CDP-choline (p<0.01). CDP-choline, but not choline, also elevated urinary MHPG significantly in rats (p<0.01). These data suggest that CDP-choline enhances norepinephrine release, and that this action may be mediated by more than just its choline content.
TL;DR: There is no obvious relationship between the ability of antidepressant treatments to alter NA turnover and decreaseΒ-adrenoceptor number and the effects of administration to rats of repeated electroconvulsive shock, clenbuterol and desipramine.
Abstract: The effects of administration to rats of repeated electroconvulsive shock (ECS), clenbuterol and desipramine (DMI) onΒ-adrenoceptor number in cortex, and noradrenaline (NA) and dopamine (DA) turnover in whole brain has been investigated by examining the rate of decline of NA concentration (kNA) following injection ofα-methyl-p-tyrosine. A single injection of clenbuterol (5 mg/kg) raised brain NA content and decreased the rate constant (kNA), leaving the turnover rate unaltered. Acute DMI injection decreased kNA and turnover rate, while a single ECS did not change NA metabolic rate. Repeated treatment with either ECS (5 seizures over 10 days), clenbuterol (5 mg/kg for 14 days) or DMI (5 mg/kg twice daily for 14 days) decreasedΒ-adrenoceptor density in cortex. No change in NA content, rate constant or turnover rate was observed after repeated ECS or clenbuterol administration. Ninety min after the last dose of DMI brain NA content was significantly decreased but kNA was unchanged compared with control animals, possibly because of the presence of subsensitive presynapticα2-adrenoceptors. At 18 hours after the last dose brain NA content was still lower than control animals but kNA was enhanced. This is presumably a “withdrawal” effect, the uptake inhibitory effect of the drug now being decreased. The treatments had little effect on DA turnover apart from DMI decreasing synthesis rate. Clearly there is no obvious relationship between the ability of antidepressant treatments to alter NA turnover and decreaseΒ-adrenoceptor number.
TL;DR: Results suggest that group differences are related to differences in carbohydrate intake and it is hypothesized that impairment of central serotonergic function due to reduced tryptophan availability can prompt mood deterioration in situations of relatively low carbohydrate intake.
Abstract: Influence of diet composition on mood during weight-reducing diets was studied in healthy young women of normal weight. A broad range of macronutrient intake was achieved by means of divergent dietary instructions for the composition of a 1,000 kcal per day diet adhered to for six weeks. Global mood during the last three weeks of the diet was significantly better in the “vegetarian” than in the “mixed” diet group. During this time a significant correlation was observed between relative carbohydrate intake and global mood (r=−0.74; p<0.01) and between the ratio of plasma tryptophan to other large neutral amino acids (a predictor of tryptophan flow into brain) and global mood (r=− 0.52; p<0.05). Results suggest that group differences are related to differences in carbohydrate intake. It is hypothesized that impairment of central serotonergic function due to reduced tryptophan availability can prompt mood deterioration in situations of relatively low carbohydrate intake.
TL;DR: Both the variable value of the DA/DA+NE ratio and the presence of DA metabolites in peripheral tissues indicate that a portion of DA may be stored outside noradrenergic neurons and directly catabolized in specific DA pools.
Abstract: Free dopamine (DA) and its metabolites, homovanillic acid (HVA) and 3–4 dihydroxyphenylacetic acid (DOPAC), have been measured and compared with norepinephrine (NE) concentrations in rat peripheral tissues using high performance liquid chromatography with electrochemical detection (HPLC-ED). Detectable amounts of DA and its metabolites were found in all the analyzed tissues. The highest levels were found in carotid body, sympathetic ganglia, urogenital tract and heart, the lowest in liver and lung. DA and DOPAC distribution was heterogeneous and unrelated to NE concentration. Both the variable value of the DA/DA+NE ratio and the presence of DA metabolites in peripheral tissues indicate that a portion of DA may be stored outside noradrenergic neurons and directly catabolized in specific DA pools.
TL;DR: The effects of theβ-carboline ZK 93426, a putative benzodiazepine receptor antagonist, were investigated in the social interaction test of anxiety and in the holeboard, finding that at higher doses of both compounds there is an attenuation of the elevation in head-dipping.
Abstract: The effects of theβ-carboline ZK 93426, a putative benzodiazepine receptor antagonist, were investigated in the social interaction test of anxiety and in the holeboard. Like the receptor antagonist Ro 15-1788, ZK 93426 (2.5–10 mg/kg) caused a specific reduction in social interaction (interpreted as an anxiogenic effect) and caused a significant elevation in exploratory head-dipping (5 mg/kg). When low (ineffective) doses of both compounds (1 mg/kg ZK 93426; 4 mg/kg Ro 15-1788) were administered together they significantly reduced social interaction. No further reductions in social interaction were observed when effective doses of both compounds (5 mg/kg ZK 93426; 10 mg/kg Ro 15-1788) were tested in combination; it is likely that this is due to almost total benzodiazepine receptor occupancy at effective doses of either compound. When doses of each compound (5 mg/kg ZK 93426; 10 mg/kg Ro 15-1788) that resulted in stimulation of head-dipping were examined in combination, the elevation in exploration was no longer observed. Since at higher doses of both compounds there is an attenuation of the elevation in head-dipping, it is again likely that the effects of the two compounds are additive.
TL;DR: L-PA had a very weak action on brain GABA levels of mice, and did not modify the rate of GABA synthesis, not compatible with a strongin vivo interaction between L-PA and GABA-mediated inhibitory transmission.
Abstract: Several previous studies have suggested a strong GABA-mimetic action of the endogenous brain imino acid, L-pipecolic acid (L-PA). In the present study, these observations were evaluated using electrophysiological and neurochemical methods. In contrast to published data our electrophysiological studies on rat cortical neuronesin situ showed only a weak, but bicuculline-sensitive depressant action of L-PA on cortical neurones. Furthermore, L-PA proved to have no affinity for any of the three components of the GABA-benzodiazepine-chloride channel receptor complex. However, using a modification of published methods a weak affinity for the GABA-B receptor site was demonstrated (IC50=1.8×10−3 M). L-PA showed no anticonvulsive activity in several tests; in particular, it did not protect mice from seizures induced by inhibition of L-glutamate-1-decarboxylase (EC 4.1.1.15: GAD). L-PA had a very weak action on brain GABA levels of mice, and did not modify the rate of GABA synthesis. In conclusion, these results are not compatible with a strongin vivo interaction between L-PA and GABA-mediated inhibitory transmission.
TL;DR: In experimentsin vitro, p-hydroxytranylcypromine was demonstrated to inhibit monoamine oxidase, although it was weaker than TCP in this regard and was a much stronger inhibitor of MAO-A than ofMAO-B.
Abstract: The formation ofp-hydroxytranylcypromine from intraperitoneally injected tranylcypromine was confirmed using two types of experiments. In the first, tranylcypromine levels were shown to be increased in brains of rats pretreated with agents known to be inhibitors of ring hydroxylation compared to rats pretreated with physiological saline. For the second set of experiments,p-nydroxytranylcypromine was identified in brain and urine (following intraperitoneal injection) by derivatizing with perfluoroacylating reagents and analyzing by electron-capture gas chromatography and by combined gas chromatography-mass spectrometry. In experimentsin vitro, p-hydroxytranylcypromine was demonstrated to inhibit monoamine oxidase, although it was weaker than TCP in this regard and was a much stronger inhibitor of MAO-A than of MAO-B.
TL;DR: The acute and chronic effects of capsaicin on the monoamines in the preoptic region + hypothalamus (RPO-H), spinal cord, substantia nigra and striatum were studied in this article.
Abstract: The acute and chronic effects of capsaicin (s.c.) on the monoamines in the preoptic region + hypothalamus (RPO-H), spinal cord, substantia nigra and striatum were studied. Levels of DOPA, DA, DOPAC, HVA, 3-MT, NA, Trp, 5-HTP, 5-HT and 5-HIAA were determined by means of liquid chromatography (HPLC-EC). In response to acute capsaicin treatment, the levels of DA, DOPAC and DA synthesis rate (DOPA formation) were increased in a dose-dependent manner in the RPO-H and spinal cord. The disappearance rate of NA was accelerated in both regions. In substantia nigra, increased DOPAC levels were found whereas the levels of 3-MT were decreased in striatum after acute capsaicin treatment. Only minor changes on the levels of 5-HT and 5-HIAA in the regions studied were noted. Neonatal or adult capsaicin treatment failed to affect the levels of NA, DA and 5-HT (measured two months or five weeks after injection, respectively) in the regions studied. A capsaicin injection to rats pretreated with the drug as adults did not affect either the monoamines in the RPO-H and spinal cord or the body temperature. In contrast, in rats pretreated with capsaicin as neonates, a second injection of the drug to adult animals elicited hypothermia and changes in monoamines similar to those observed in naive animals.
TL;DR: The findings agree with previous reports on the stereoselectivity of monoaminergic mechanisms toward TCP enantiomers, and support the notion that the 5-HT uptake site may be associated with the imipramine binding site.
Abstract: Studies were carried outin vitro to determine effects of tranylcypromine enantiomers ([+]- and [−]-TCP) on uptake and release of 5-HT, DA and NA in rat synaptosomes and on imipramine binding to rabbit platelets. (+)-TCP was more potent than (−)-TCP as inhibitor of 5-HT uptake and imipramine binding, whereas (−)-TCP was more potent than (+)-TCP as inhibitor of DA and NA uptake. The enantiomers differed only slightly in their effects on monoamine release. The findings agree with previous reports on the stereoselectivity of monoaminergic mechanisms toward TCP enantiomers, and support the notion that the 5-HT uptake site may be associated with the imipramine binding site.
TL;DR: Intravenously applied iron-in form of a ferri-ferro-complex-exhibited a considerable benefit for all patients treated so far and regained a remarkable mobility.
Abstract: One of the problems in treating Parkinson patients is the so called “off-effect” which occurs after long term treatment with L-DOPA Off-effects are characterized by severe rigor and akinesia Increasing dosages of L-DOPA and decarboxylase- or monoaminooxidase-inhibitors do not improve these symptoms Intravenously applied iron-in form of a ferri-ferro-complex-exhibited a considerable benefit for all patients treated so far They regained a remarkable mobility Their disability score dropped from up to 90% down to 30% The effect of iron is dosage-dependent and lasts 24 to 48 hours