Brain Dopamine Levels Research Articles

Central Injection of Glucose Modifies Behavior, Amino Acid and Monoamine Metabolism in Neonatal Chicks under Acute Stressful Conditions.

The effect of intracerebroventricular (i.c.v.) injection of a wide range of glucose concentrations on the behavioral response, central amino acid and monoamine contents was investigated in chicks exposed to a social isolation stressful condition. The chicks were given an i.c.v. injection of 0.21, 0.42, 0.84, and 1.68 µmol of D-glucose, and then behavioral changes were observed over 10 min. The behavioral stress response was dose-dependently decreased and calm behavior was increased by i.c.v. administration of glucose. In the diencephalon, glutamine was positively correlated, whereas glycine was negatively correlated with the dose of glucose. In the telencephalon, the dopamine metabolite and dopamine turnover rates were positively correlated, whereas dopamine was negatively correlated with doses of glucose. In the plasma, isoleucine and hydroxyproline were positively correlated with the dose of glucose, and several amino acids were also influenced by glucose levels.These results suggest that the possible pathways of the sedative effect of glucose include: (1) amino acids synthesized from injected glucose, which can induce the sedative and/or hypnotic effects; (2) amino acids modified by injected glucose transported in the brain from the peripheral tissues; and (3) injected glucose-induced decreases in brain dopamine levels. In conclusion, these changes induced by central glucose interact and induce the sedative effect in neonatal chicks.

Social dominance and reproductive differentiation mediated by dopaminergic signaling in a queenless ant.

In social Hymenoptera with no morphological caste, a dominant female becomes an egg layer, whereas subordinates become sterile helpers. The physiological mechanism that links dominance rank and fecundity is an essential part of the emergence of sterile females, which reflects the primitive phase of eusociality. Recent studies suggest that brain biogenic amines are correlated with the ranks in dominance hierarchy. However, the actual causality between aminergic systems and phenotype (i.e. fecundity and aggressiveness) is largely unknown due to the pleiotropic functions of amines (e.g. age-dependent polyethism) and the scarcity of manipulation experiments. To clarify the causality among dominance ranks, amine levels and phenotypes, we examined the dynamics of the aminergic system during the ontogeny of dominance hierarchy in the queenless ant Diacamma sp., which undergoes rapid physiological differentiation based on dominance interactions. Brain dopamine levels differed between dominants and subordinates at day 7 after eclosion, although they did not differ at day 1, reflecting fecundity but not aggressiveness. Topical applications of dopamine to the subordinate workers induced oocyte growth but did not induce aggressiveness, suggesting the gonadotropic effect of dopamine. Additionally, dopamine receptor transcripts (dopr1 and dopr2) were elevated in the gaster fat body of dominant females, suggesting that the fat body is a potential target of neurohormonal dopamine. Based on this evidence, we suggest that brain dopamine levels are elevated in dominants as a result of hierarchy formation, and differences in dopamine levels cause the reproductive differentiation, probably via stimulation of the fat body.

Simplified dietary acute tryptophan depletion: effects of a novel amino acid mixture on the neurochemistry of C57BL/6J mice

BackgroundDiet and nutrition can impact on the biological processes underpinning neuropsychiatric disorders. Amino acid (AA) mixtures lacking a specific neurotransmitter precursor can change the levels of brain serotonin (5-HT) or dopamine (DA) in the central nervous system. The availability of these substances within the brain is determined by the blood–brain barrier (BBB) that restricts the access of peripheral AA into the brain. AA mixtures lacking tryptophan (TRP) compete with endogenous TRP for uptake into the brain across the BBB, which in turn leads to a decrease in central nervous 5-HT synthesis.ObjectiveThe present study compared the effects of a simplified acute tryptophan depletion (SATD) mixture in mice on blood and brain serotonergic and dopaminergic metabolites to those of a commonly used acute tryptophan depletion mixture (ATD Moja-De) and its TRP-balanced control (BAL).DesignThe SATD formula is composed of only three large neutral AAs: phenylalanine (PHE), leucine (LEU), and isoleucine (ILE). BAL, ATD Moja-De, or SATD formulas were delivered to adult male C57BL/6J mice by gavage. TRP, monoamines, and their metabolites were quantified in blood and brain regions (hippocampus, frontal cortex, amygdala, caudate putamen, and nucleus accumbens).ResultsBoth ATD Moja-De and SATD significantly decreased levels of serum and brain TRP, as well as brain 5-HIAA and 5-HT compared with BAL. SATD reduced HVA levels in caudate but did not alter total DA levels or DOPAC. SATD decreased TRP and serotonergic metabolites comparably to ATD Moja-De administration.ConclusionA simplified and more palatable combination of AAs can manipulate serotonergic function and might be useful to reveal underlying monoamine-related mechanisms contributing to different neuropsychiatric disorders.

Selective Lifelong Destruction of Brain Monoaminergic Nerves Through Perinatal DSP-4 Treatment.

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a highly selective neurotoxin for noradrenergic projections originating from the locus coeruleus (LC). The outcome of the systemic DSP-4 treatment of newborn rats is an alteration in postnatal development of the noradrenergic system, involving the permanent denervation of distal noradrenergic projection areas (neocortex, hippocampus, spinal cord), accompanied by noradrenergic hyperinnervation in regions proximal to the LC cell bodies (cerebellum, pons-medulla). DSP-4 is well tolerated by developing rats and does not increase the mortality rate. Permanent noradrenergic denervation in the cerebral cortex and spinal cord is present at all developmental stages, although this effect is more pronounced in rats treated with DSP-4 at an early age, i.e., up to postnatal day 5 (PND 5). Notably, regional hyperinnervation is a hallmark of neonatal DSP-4 treatment, which is not observed after either prenatal or adult DSP-4 application. In contrast to robust biochemical changes in the brain, DSP-4 treatment of newborn rats has a marginal effect on arousal and cognition functions assessed in adulthood, and these processes are critically influenced by the action of the noradrenergic neurotransmitter, norepinephrine (NE). Conversely, neonatal DSP-4 does not significantly affect 5-hydroxytryptamine (serotonin; 5-HT), dopamine (DA), gamma-aminobutyric acid (GABA), and histamine levels in brain. However, as a consequence of altering the functional efficacy of 5-HT1A, 5-HT1B, DA, and GABA receptors, these neurotransmitter systems are profoundly affected in adulthood. Thus, the noradrenergic lesion obtained with neonatal DSP-4 treatment represents a unique neurobiological technique for exploring the interplay between various neuronal phenotypes and examining the pathomechanism of neurodevelopmental disorders.

L-Dopa improves learning and maintenance of new nouns in healthy adults

Event Abstract Back to Event L-Dopa improves learning and maintenance of new nouns in healthy adults David Copland1*, Alana Campbell2, Alicia Rawlings3, Katie McMahon4, Peter Silburn5 and Pradeep Nathan6 1 The University of Queensland, UQ Centre for Clinical Research & School of Health and Rehabilitation Sciences, Australia 2 The University of Queensland, School of Health & Rehabilitation Sciences, Australia 3 The University of Queensland, UQ Centre for Clinical Research, Australia 4 The University of Queensland, Centre for Advanced Imaging, Australia 5 The University of Queensland, Asia Pacific Centre for Neuromodulation, Australia 6 Cambridge University, Psychiatry, United Kingdom Background: L-Dopa is a dopamine precursor that has been shown to improve implicit word learning in healthy adults. L-Dopa has also been shown to modulate semantic processing and enhance semantic salience, which may be of relevance to mechanisms of new word learning. The present study aimed to investigate whether augmenting brain dopamine levels with L-Dopa would enhance new word learning in healthy adults. We also sought to evaluate whether words paired with semantic information would be learnt more effectively than words paired with non-semantic information, and whether L-Dopa would enhance this process. Methods: 21 (12 female) healthy young adults participated in an initial word learning session. Prior to the learning session, each participant received either L-Dopa (as Madopar 125mg) or placebo in a double-blind randomised design. Participants learned written names for 20 pictures of novel aliens, with each name consisting of a legal nonword and either two adjectives (the semantic condition) or two uncommon surnames (the non-semantic condition). Written recall and multiple-choice recognition of the new names was tested periodically during the learning session, and at a follow-up session 7-10 days later. Results: Participants who had taken L-Dopa prior to learning exhibited higher recall accuracy during the learning session and at follow-up than those who had taken placebo. There was no influence of learning condition (Semantic or Non-Semantic) on recall accuracy at either timepoint. However, there was an influence of learning condition on recognition accuracy at the follow-up session, with the L-Dopa group displaying greater accuracy for stimuli in the semantic condition than the placebo group. This effect was not observed for stimuli in the non-semantic condition. Conclusions: L-Dopa improved the speed and success of new word learning, and also improved retention of the new words. The difference observed in recognition performance between the two groups at follow-up suggests that the influence of increased dopamine on the consolidation of new lexical representations is enhanced by semantic information during encoding. Keywords: Dopamine, Language, Memory, semantics, word learning Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Memory and Learning Citation: Copland D, Campbell A, Rawlings A, McMahon K, Silburn P and Nathan P (2015). L-Dopa improves learning and maintenance of new nouns in healthy adults. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00165 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Prof. David Copland, The University of Queensland, UQ Centre for Clinical Research & School of Health and Rehabilitation Sciences, Brisbane, Australia, d.copland@uq.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers David Copland Alana Campbell Alicia Rawlings Katie McMahon Peter Silburn Pradeep Nathan Google David Copland Alana Campbell Alicia Rawlings Katie McMahon Peter Silburn Pradeep Nathan Google Scholar David Copland Alana Campbell Alicia Rawlings Katie McMahon Peter Silburn Pradeep Nathan PubMed David Copland Alana Campbell Alicia Rawlings Katie McMahon Peter Silburn Pradeep Nathan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Choosing money over drugs: The underpinnings of rational choice in cocaine addicts

Aims: One way to predict if an adolescent will initiate drug use is whether or not their peers use drugs. In animals, social facilitation of drug taking behavior is only beginning to be understood. Recent work indicated that adolescent rats raised in isolated conditions find social interactions to be highly rewarding, especially in males. In a recent study in our laboratory, we found that individually housed adolescent male rats showed a conditioned place preference (CPP) for a compartment paired previously with a social partner. This social reward reduced amphetamine reward when rats were allowed choice between a socialand drug paired compartment concurrently. The current experiment tested the hypothesis that social interaction may compete with amphetamine reward by activating similar neural systems. Methods:Male adolescent Sprague Dawley rats (28 days of age, n=16) were habituated to a CPP apparatus chamber for 30min on the first session. The next session, half of the subjects were placed into a chamber alone for 30min, while the other half were paired with a same-age male conspecific for 30min. Immediately following the session, brains were dissected intomedial prefrontal cortex (mPFC), dorsal striatum, nucleus accumbens (NAcc), and hypothalamus; brain levels of dopamine, DOPAC, 5-HT, and 5-HIAA were quantified by HPLC-EC. Results:Results for dopamine utilization (DOPAC/DA) showed a main effect of brain region [F(3,10) =88.957, p<0.001] and a main effect of socialization [F(1,12) =21.697, p=0.001], with dopamine utilization elevated by social interaction across all regions. No significant effect of social interaction was observed with 5-HT utilization in any brain region examined. Conclusions: These results indicate that social interaction activates mesocorticolimbic dopamine systems and that this neural activation may blunt the rewarding effect of amphetamine in adolescent male rats. Financial support: Funding provided by NIH grants P50 DA05312 and T32 DA016176 and R01 DA12964.

Curcumin's neuroprotective efficacy in Drosophila model of idiopathic Parkinson's disease is phase specific: implication of its therapeutic effectiveness.

Selective degeneration of dopaminergic neurons in the substantia nigra underlies the basic motor impairments of Parkinson's disease (PD). Curcumin has been used for centuries in traditional medicines in India. Our aim is to understand the efficacy of genotropic drug curcumin as a neuroprotective agent in PD. Analysis of different developmental stages in model organisms revealed that they are characterized by different patterns of gene expression which is similar to that of developmental stages of human. Genotropic drugs would be effective only during those life cycle stages for which their target molecules are available. Hence there exists a possibility that targets of genotropic compounds such as curcumin may not be present in all life stages. However, no reports are available in PD models illustrating the efficacy of curcumin in later phases of adult life. This is important because this is the period during which late-onset disorders such as idiopathic PD set in. To understand this paradigm, we tested the protective efficacy of curcumin in different growth stages (early, late health stage, and transition phase) in adult Drosophila flies. Results showed that it can rescue the motor defects during early stages of life but is ineffective at later phases. This observation was substantiated with the finding that curcumin treatment could replenish depleted brain dopamine levels in the PD model only during early stages of life cycle, clearly suggesting its limitation as a therapeutic agent in late-onset neurodegenerative disorders such as PD.

Consumption of tyrosine in royal jelly increases brain levels of dopamine and tyramine and promotes transition from normal to reproductive workers in queenless honey bee colonies

Dopamine (DA) and tyramine (TA) have neurohormonal roles in the production of reproductive workers in queenless colonies of honey bees, but the regulation of these biogenic amines in the brain are still largely unclear. Nutrition is an important factor in promoting reproduction and might be involved in the regulation of these biogenic amines in the brain. To test this hypothesis, we examined the effect of oral treatments of tyrosine (Tyr; a common precursor of DA, TA and octopamine, and a component of royal jelly) in queenless workers and quantified the resulting production of biogenic amines. Tyrosine treatments enhanced the levels of DA, TA and their metabolites in the brain. Workers fed royal jelly had significantly larger brain levels of Tyr, DA, TA and the metabolites in the brains compared with those bees fed honey or sucrose (control). Treatment with Tyr also inhibited the behavior of workers outside of the hive and promoted ovarian development. These results suggest that there is a link between nutrition and the regulation of DA and TA in the brain to promote the production of reproductive workers in queenless honey bee colonies.

Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice

Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation.

Effects of low dose endosulfan exposure on brain neurotransmitter levels in the African clawed frog Xenopus laevis

Understanding the impact of pesticides in amphibians is of growing concern to assess the causes of their decline. Among pesticides, endosulfan belongs to one of the potential sources of danger because of its wide use and known effects, particularly neurotoxic, on a variety of organisms. However, the effect of endosulfan was not yet evaluated on amphibians at levels encompassing simultaneously brain neurotransmitters and behavioural endpoints. In this context, tadpoles of the African clawed frog Xenopus laevis were submitted to four treatments during 27d: one control, one ethanol control, and two low environmental concentrations of endosulfan (0.1 and 1μgL−1). Endosulfan induced a significant increase of brain serotonin level at both concentrations and a significant increase of brain dopamine and GABA levels at the lower exposure but acetylcholinesterase activity was not modified by the treatment. The gene coding for the GABA transporter 1 was up-regulated in endosulfan contaminated tadpoles while the expression of other genes coding for the neurotransmitter receptors or for the enzymes involved in their metabolic pathways was not significantly modified by endosulfan exposure. Endosulfan also affected foraging, and locomotion in links with the results of the physiological assays, but no effects were seen on growth. These results show that low environmental concentrations of endosulfan can induce adverse responses in X. laevis tadpoles. At a broader perspective, this suggests that more research using and linking multiple markers should be used to understand the complex mode of action of pollutants.

Rationale and design of REWARD (revving-up exercise for sustained weight loss by altering neurological reward and drive): A randomized trial in obese endometrial cancer survivors

BackgroundObesity is a leading risk factor for endometrial cancer (EC), particularly Type I forms, which are increasing in the U.S. Although death rates from most cancers have been decreasing, overall mortality in EC is increasing in the U.S. EC survivors' poor fitness combined with their surgical treatments may make weight loss particularly challenging. High intensity exercise increases neurotrophins and neurological reward via altered striatal dopamine in animals, and, in humans, chronic high intensity exercise enhances meal-induced satiety and may reduce hedonic eating. “Assisted” exercise, a mode of exercise whereby a patient's voluntary exercise rate is augmented mechanically, may modulate brain dopamine levels in Parkinson's Disease patients but has not been previously evaluated as a treatment for obesity. MethodsWe describe the rationale and design of the REWARD trial, which has the overarching goal of randomizing 120 obese EC survivors to “assisted” or voluntary rate cycling to evaluate the efficacy of “assisted” exercise in enhancing and sustaining weight loss. Patients in both arms will receive 3days/week of supervised exercise and 1day/week of a group dietary behavioral intervention for 16weeks and, then, will be followed for 6months. OutcomesThe primary outcome is weight loss. Secondary outcomes include measures for body composition, fitness, eating behavior, exercise motivation and, quality of life as well as cognition and food reward and motivation as assessed by functional magnetic resonance imaging (fMRI) tasks. ConclusionsIf successful, the REWARD program could be extended to help sustain weight loss in obese cancer and non-cancer patients.

Anti-Epileptic and Anti-Psychotic Effects of Ipomoea reniformis (Convolvulaceae) in Experimental Animals

Ipomoea reniformis (IR) Choisy is claimed in Indian traditional medical practice to be useful in the treatment of epilepsy and neurological disorders. In the present study, methanolic extract of IR was evaluated for anti-epileptic and anti-psychotic activities in rodent models using standard procedures. Besides evaluating epileptic and behavioural parameters, neurotransmitters such as gamma-amino butyric acid (GABA) in epilepsy and in psychosis, dopamine, noradrenaline and serotonin contents were estimated in the rodent brain. IR extract pretreatment for 15 days reduced maximal electro shock, isonicotinyl hydrazine (INH) and pentylenetetrazole (PTZ)-induced seizures and also significantly inhibited the attenuation of brain GABA levels by INH and PTZ in mice. These findings suggest that the observed beneficial effect of IR extract in epilepsy may be by enhancing the GABAergic system. The extract also inhibited apomorphine-induced climbing and stereotyped behaviours and showed significantly reduced levels of brain dopamine, noradrenaline and serotonin which may be due to blocking of central dopaminergic, noradrenergic and serotonergic pathways or by enhancing the GABAergic system. The results of the present study suggest that the title plant possesses anti-epileptic and anti-psychotic activities in rodents.

Augmentation of antidepressant effects of duloxetine and bupropion by caffeine in mice

There is an unmet need in the treatment of depression suggesting requirement of new therapeutic approaches having better efficacy and safety profile. Patients receiving antidepressant therapy generally consume caffeine in the form of tea or coffee. The objective of the present study was to evaluate the augmentation of antidepressant effects of duloxetine and/or bupropion with caffeine. Male Swiss Albino mice received treatment of normal saline (10ml/kg), ‘caffeine alone’ (10mg/kg), ‘duloxetine alone’ (10mg/kg), ‘bupropion alone’ (10mg/kg), caffeine+duloxetine (5mg/kg, each), bupropion+caffeine (5mg/kg, each), and bupropion+duloxetine (5mg/kg, each) through the intra-peritoneal route. The immobility period was analyzed 30min after the treatment in forced swim and tail suspension tests. Norepinephrine, dopamine, and serotonin levels were analyzed in hippocampus, cerebral cortex and whole brain using HPLC with fluorescence detector. Euthanasia was performed 1h after treatment. Comparison between vehicle treated group and other groups showed significant decrease in immobility in all drug treated groups in both antidepressant models. Caffeine plus duloxetine treated group was better among the combination treated groups in terms of decrease in immobility and increase in norepinephrine, dopamine, and serotonin levels in hippocampi, cerebral cortices, and whole brain when compared to their respective monotherapy treated groups. These combination approaches may help in reducing the dose of duloxetine/bupropion, and consequently lower the associated side/adverse effects.

Scaling and coordination deficits during dynamic object manipulation in Parkinson's disease

The ability to reach for and dynamically manipulate objects in a dexterous fashion requires scaling and coordination of arm, hand, and fingertip forces during reach and grasp components of this behavior. The neural substrates underlying dynamic object manipulation are not well understood. Insight into the role of basal ganglia-thalamocortical circuits in object manipulation can come from the study of patients with Parkinson's disease (PD). We hypothesized that scaling and coordination aspects of motor control are differentially affected by this disorder. We asked 20 PD patients and 23 age-matched control subjects to reach for, grasp, and lift virtual objects along prescribed paths. The movements were subdivided into two types, intensive (scaling) and coordinative, by detecting their underlying self-similarity. PD patients off medication were significantly impaired relative to control subjects for both aspects of movement. Intensive deficits, reduced peak speed and aperture, were seen during the reach. Coordinative deficits were observed during the reach, namely, the relative position along the trajectory at which peak speed and aperture were achieved, and during the lift, when objects tilted with respect to the gravitational axis. These results suggest that basal ganglia-thalamocortical circuits may play an important role in fine motor coordination. Dopaminergic therapy significantly improved intensive but not coordinative aspects of movements. These findings are consistent with a framework in which tonic levels of dopamine in the dorsal striatum encode the energetic cost of a movement, thereby improving intensive or scaling aspects of movement. However, repletion of brain dopamine levels does not restore finely coordinated movement.

Effects of gypenosides on anxiety disorders in MPTP-lesioned mouse model of Parkinson׳s disease

Ethanol extract (GP-EX) of Gynostemma pentaphyllum (GP) ameliorates chronic stress-induced anxiety in mice. The present study investigated the effects of gypenoside-enriched components (GPS), GP-EX and water extract of GP (GP-WX) on MPTP lesion-induced affective disorders in C57BL/6 mice. GPS (50mg/kg) and GP-EX (50mg/kg) for 21 day-treatment period improved the symptom of anxiety disorders in the MPTP-lesioned mouse model of PD with or without l-DOPA treatment, which was examined by the elevated plus-maze and marble burying tests. In these states, treatments with GPS (50mg/kg) and GP-EX (50mg/kg) significantly increased the brain levels of dopamine and serotonin in the MPTP-lesioned mouse model of PD with or without l-DOPA treatment. In addition, treatments with GPS (50mg/kg) and GP-EX (50mg/kg) showed protective effects on dopaminergic neurons in MPTP-lesioned mouse model of PD with or without l-DOPA treatment. In contrast, GPS (30mg/kg) and GP-WX (50mg/kg) showed anxiolytic effects in the same animal models, but it was not significant. These results suggest that GPS (50mg/kg) and GP-EX (50mg/kg) showed anxiolytic effects on affective disorders and protective effects on dopaminergic neurons by modulating the brain levels of dopamine and serotonin in the MPTP-lesioned mouse model of PD with or without l-DOPA treatment. Clinical trials of GPS and GP-EX need to be conducted further so as to develop adjuvant therapeutic agents for PD patients.

Environmental enrichment induces changes in brain monoamine levels in gilthead seabream Sparus aurata

It is generally accepted that environmental enrichment enhances the performance and improves welfare of animals kept in captivity. Similar results have been obtained for fish. It has been previously reported that the presence of Blue or Red-Brown Substrate (BS and RBS respectively) on tank bottom resulted in growth enhancement and suppression of aggressive behavior of gilthead seabream Sparus aurata compared to Green Substrate (GS) and tanks without modifications (Control-C). In an attempt to identify the underlying mechanisms, in the present study the effects of this environmental enrichment on brain monoamine neurotransmitters and fatty acids of gilthead seabream were evaluated. BS and RBS fish had lower serotonergic activity (5-HIAA/5-HT), resulting mainly from lower 5-hydroxyindoleacetic acid (5-HIAA) levels. BS fish also had lower serotonin levels compared to all other treatments. Brain noradrenaline (NA) levels did not show significant differences between substrate treatments and control. Brain dopamine (DA) levels were lowest in BS and RBS fish, higher in GS fish and highest in C fish. No differences were observed for dopamine metabolites or dopaminergic activity. Moreover, brain NA was negatively correlated with body weight in BS fish and positively correlated in RBS and C fish. A positive correlation was also observed for brain DA with body weight in RBS fish. No differences were observed for brain fatty acids. Present results support the hypothesis that the beneficial effects of the presence of BS and RBS are related to altered social interactions and indicate the establishment of a less stressful social organization in enriched-reared fish groups.

RETRACTED: Do adipose tissue-derived mesenchymal stem cells ameliorate Parkinson’s disease in rat model?

Parkinson's disease (PD) is a common neurodegenerative disorder in middle-aged and elderly people. This study aimed to elucidate the role of mesenchymal stem cells (MSCs) in management of PD in ovariectomized rat model. MSCs were excised from adipose tissue of both the omentum and the inguinal fat pad of male rats, grown, and propagated in culture; then characterized morphologically; and by the detection of surface markers gene expression. In this study, 40 ovariectomized animals were classified into 5 groups; group 1 was ovariectomized control, groups 2 to 5 were subcutaneously administered with rotenone for 14 days after 1 month of ovariectomy for induction of PD. Group 2 was left untreated; groups 3, 4, and 5 were treated with Sinemet(®), Cerebrolysin(®), and a single dose of adipose tissue-derived MSCs (ADMSCs), respectively. Y-chromosome gene (sry) was assessed by polymerase chain reaction (PCR) in brain tissue of the female rats. Serum transforming growth factor β (TGF-β), monocyte chemoattractant protein 1 (MCP-1), and brain-derived neurotrophic factor (BDNF) levels were assayed using enzyme-linked immunosorbent assay technique. Brain dopamine level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) gene expression was detected by semiquantitative real-time PCR. The PD group showed significant increase in serum TGF-β and MCP-1 levels associated with significant decrease in serum BDNF, brain dopamine, and brain TH gene expression levels. In contrast, all treatments produce significant decrease in serum TGF-β and MCP-1 levels in concomitant with significant increase in serum BDNF, brain dopamine, and brain TH gene expression levels. In conclusion, the observed improvements in the studied biomarkers due to ADMSCs infusion might be attributed to their immunomodulatory, anti-inflammatory, and neurotrophic effects.

Antidepressant effect of linseed oil on various behavioral and pharmacological models of depression in Swiss albino mice

Background: Linum usitatissimum Linn. (Linaceae) commonly known as linseed or flaxseed is known to be the richest plant source for alpha-linoleic acid, an omega-3 fatty acid. Aim: The objective of the present study was to evaluate the oil extracted from Linseed (LO) for anti-depressant activity in mice. Materials and Methods: Healthy male Swiss albino mice were randomly divided into five groups as follows: (i) Control, (ii) LO (4 ml/kg b.w./day), (iii) LO (8 ml/kg/day), (iv) Fish oil (FO) equivalent to 300 mg/kg/day of Docosahexaenoic acid (DHA), and (v) Standard (Imipramine). The antidepressant effect was evaluated using behavioral models like the Despair swim test (DST) and Tail suspension test (TST), and pharmacological models like potentiation of norepinephrine toxicity, 5-hydroxytryptophan potentiation, tetrabenazine antagonism, and apomorphine-induced cage climbing. Fluorimetric estimation of norepinephrine, dopamine, and 5-hydroxytryptophan levels in the brain was also carried out. Results: In case of behavioral models, LO at 0.2 ml/mice/day, significantly reduced the immobilization time. A significant antidepressant activity of LO was found in the pharmacological models. This was confirmed by the elevated levels of norepinephrine and dopamine in the brains of LO-treated animals, as compared to control animals. Conclusion: Linseed oil showed a significant antidepressant effect in various experimental models of depression in Swiss mice, which seemed most likely to be mediated through an interaction with the adrenergic and dopaminergic systems.

Methylphenidate decreases fat and carbohydrate intake in obese teenagers

Dopamine is a neurotransmitter that mediates the reward value of food. Methylphenidate (MPH) selectively binds and inhibits the dopamine transporter, thus increasing brain dopamine levels shortly after oral administration. This investigation studied whether a single dose of MPH decreases energy intake (EI) in obese teenagers compared to placebo (P). This study used a single-blind, placebo-controlled, within subject design. Teenagers with body mass index (BMI) ≥95th percentile underwent two identical meal tests (P or MPH) after a 10 h fast in random order. Food was weighed before and after the meals, and EI was calculated as energy content/gram of consumed foods. Total and macronutrient EI (mean ± SD) were analyzed by Mann-Whitney U and Wilcoxon tests. Twenty-two subjects (15 females, 7 males) completed the study. Participants were 13.4 ± 2.2 years old and had BMI 34.9 ± 10.7 kg/m². EI from fat (167 vs. 203 kcal, P = 0.03) and carbohydrates (311 vs. 389 kcal, P = 0.04) was decreased for MPH compared to P meals, with a trend in decreased total EI (545 vs. 663 kcal, P = 0.06). A single dose of MPH decreases EI from fat and carbohydrates in obese adolescents. This effect underscores the importance of central dopamine signaling on eating behavior.

Hypodopaminergic mice have a sleep phenotype that resembles human Parkinson’s disease

Introduction Patients with Parkinson’s Disease (PD) have markedly disturbed sleep. For example, they have difficulty falling and staying asleep, and they commonly experience motor disturbances during both NREM and REM sleep (e.g., RBD). PD patients also suffer from excessive daytime sleepiness and in some cases experience sleep attacks. Although multiple animal models have been used to understand how abnormal dopamine transmission contributes to the cognitive and motor abnormalities in PD, none of them have determined if sleep is impacted in these models. Our current goal was to determine if an established mouse model of PD exhibits a sleep phenotype that resembles PD in human patients. The present study was designed to determine if hypodopaminergic (i.e., reduced brain levels of dopamine) mice have abnormal sleep and waking activity patterns that recapitulate sleep-wake activity in human PD patients. Materials and methods We used both wild-type mice (WT, n = 4) and transgenic mice overexpressing the dopamine transporter (DAT-tg, n = 4). DAT-tg mice experience a 40% reduction in striatal dopamine levels and are an established model of PD. For example, they have significantly reduced brain levels of dopamine similar to that in human PD. DAT-Tg and WT mice were implanted with standard EEG and EMG electrodes for recording wakefulness, NREM and REM sleep. To determine if DAT-tg experience sleep-wake disturbs EEG and EMG activity was recorded for 24 h. Both WT and DAT-tg were habituated to recording instrumentation for 1 day before experimental testing began. results DAT-tg mice exhibit a PD phenotype. They suffer from sleepiness, disturbed sleep patterns and most notably experience sleep attacks. Compared to WT, which never experienced sleep attacks, we found that DAT-tg mice rapidly transitioned directly from active (not quiet) wakefulness into full-blown NREM sleep. Sleep attacks could result from their persistent sleepiness. DAT-tg mice experienced a 110% increase overall levels of NREM sleep compared to WT mice. REM sleep amounts were similar in both groups of mice. DAT-tg mice also suffered from sleep fragmentation. Compared to WT mice, they experienced a 184% increase in the total number of NREM sleep episodes. Conclusion As hypothesized, DAT-tg mice exhibit a PD phenotype. They suffer from persistent sleepiness, have disturbed sleep patterns and experience sleep attacks. These mice are therefore a suitable model for dissecting the mechanisms associated with sleep disturbs in human PD. Acknowledgements The present work was supported by CIHR grant.