Changes In Brain Monoamine Levels Research Articles

Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities.

Rett syndrome (RTT) is a neurodevelopmental disorder with X-linked dominant inheritance caused mainly by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The effects of various Mecp2 mutations have been extensively assessed in mouse models, but none adequately mimic the symptoms and pathological changes of RTT. In this study, we assessed the effects of Mecp2 gene deletion on female rats (Mecp2+/-) and found severe impairments in social behavior [at 8 weeks (w), 12 w, and 23 w of age], motor function [at 16 w and 26 w], and spatial cognition [at 29 w] as well as lower plasma insulin-like growth factor (but not brain-derived neurotrophic factor) and markedly reduced acetylcholine (30%-50%) in multiple brain regions compared to female Mecp2+/+ rats [at 29 w]. Alternatively, changes in brain monoamine levels were relatively small, in contrast to reports on mouse Mecp2 mutants. Female Mecp2-deficient rats express phenotypes resembling RTT and so may provide a robust model for future research on RTT pathobiology and treatment.

Effect of short- and long-term heat exposure on brain monoamines and emotional behavior in mice and rats

Heat exposure affects several physiological, neuronal, and emotional functions. Notably, monoaminergic neurotransmitters in the brain such as noradrenaline, dopamine, and serotonin, which regulate several basic physiological functions, such as thermoregulation, food intake, and energy balance, are affected by heat exposure and heat acclimation. Furthermore, cognition and emotional states are also affected by heat exposure and changes in brain monoamine levels. Short-term heat exposure has been reported to increase anxiety in some behavioral tests. In contrast, there is a possibility that long-term heat exposure decreases anxiety due to heat acclimation. These changes might be due to adaptation of the core body temperature and/or brain monoamine levels by heat exposure. In this review, we first outline the changes in brain monoamine levels and thereafter focus on changes in emotional behavior due to heat exposure and heat acclimation. Finally, we describe the relationships between emotional behavior and brain monoamine levels during heat acclimation.

Neurotoxicity Induced by Mephedrone: An up-to-date Review.

Mephedrone is a β-ketoamphetamine belonging to the family of synthetic cathinones, an emerging class of designer drugs known for their hallucinogenic and psychostimulant properties as well as for their abuse potential. The aim of this review was to examine the emerging scientific literature on the possible mephedrone-induced neurotoxicity, yet not well defined due to the limited number of experimental studies, mainly carried on animal models. Relevant scientific articles were identified from international literature databases (Medline, Scopus, etc.) using the keywords: “Mephedrone”, “4-MMC,” “neurotoxicity,” “neuropharmacology”, “patents”, “monoamine transporters” and “neurochemical effects”. Of the 498 sources initially found, only 36 papers were suitable for the review. Neurotoxic effect of mephedrone on 5-HT and DA systems remains controversial. Although some studies in animal models reported no damage to DA nerve endings in the striatum and no significant changes in brain monoamine levels, some others suggested a rapid reduction in 5-HT and DA transporter function. Persistent serotonergic deficits were observed after binge like treatment in a warm environment and in both serotonergic and dopaminergic nerve endings at high ambient temperature. Oxidative stress cytotoxicity and an increase in frontal cortex lipid peroxidation were also reported. In vitro cytotoxic properties were also observed, suggesting that mephedrone may act as a reductant agent and can also determine changes in mitochondrial respiration. However, due to the differences in the design of the experiments, including temperature and animal model used, the results are difficult to compare. Further studies on toxicology and pharmacology of mephedrone are therefore necessary to establish an appropriate treatment for substance abuse and eventual consequences for public health.

Voluntary exercise and increased food intake after mild chronic stress improve social avoidance behavior in mice

It is well-established that exercise can influence psychological conditions, cognitive function, and energy metabolism in peripheral tissues including the skeletal muscle. However, it is not clear whether exercise can influence social interaction with others and alleviate defeat stress. This study investigated the effect of voluntary wheel running on impaired social interaction induced by chronic social defeat stress (SDS) using the resident–intruder social defeat model. Mice were divided into three groups: control, stress alone, and stress+exercise. SDS was performed by exposing C57BL/6 mice to retired ICR mice for 2.5min. The C57BL/6 mice were continuously defeated by these resident (aggressor) mice and, following 5days of SDS, experienced 2days of rest with no SDS. Mice in the stress+exercise group were allowed to voluntarily run on a wheel for 2h after every SDS exposure. Two weeks later, compared to the control group, the stress group showed a higher ratio of time spent in the corner zone of a social interaction paradigm even though SDS did not elicit depressive- and anxiety-like behaviors. We also observed that voluntary exercise, which did not affect muscle weight and gene expression, decreased social avoidance behavior of stressed mice without clear changes in brain monoamine levels. Interestingly, food intake in the stress+exercise group was the greatest among the three groups. To test the effect of the exercise-induced increase in food intake on social behavior, we set up a pair-fed group where food intake was restricted. We then compared these mice to mice in the stress alone group. We found that the ratio of time spent in the corner zone of the social interaction test was not different between ad libitum- and pair-fed groups, although pair-fed mice spent more time in the corner zone when an aggressor mouse was present than when it was absent. In addition, pair-feeding did not show exercise-induced reductions of adrenal gland weight and enhanced the loss of body fat. Our findings indicate that voluntary exercise reduces social avoidance behavior induced by SDS. Further, we determined that SDS and exercise-induced increases in food intake partially influence energy metabolism and social avoidance behavior.

Cocaine enhances the conditioned rewarding effects of MDMA in adolescent mice.

Although the consumption of cocaine is frequent in young users of MDMA (3,4-methylenedioxymethamphetamine), the influence of exposure to cocaine on the rewarding effects of MDMA in adolescents has not been studied. The purpose of the present work was to evaluate the effect of co-administration of cocaine (1 and 10 mg/kg) and a sub-threshold dose of MDMA (1.25 mg/kg) on the acquisition of conditioned place preference (CPP) (experiment 1). In addition, the effect of pre-treatment with cocaine on MDMA-induced CPP was evaluated (experiment 2). Levels of monoamines in striatum, hippocampus and cortex were measured in both experiments. Our hypotheses were that cocaine co-administration or pre-treatment would increase the rewarding effects of MDMA, and that these effects would be related with changes in brain monoamine levels. Our results showed that cocaine potentiated the rewarding effects of MDMA, since a sub-threshold dose of MDMA, which did not induce CPP by itself, induced a significant CPP in adolescent mice when administered along with cocaine during conditioning (experiment 1). Moreover, pre-treatment with cocaine several days before conditioning also increased the rewarding effects of MDMA (experiment 2). No significant changes in the levels of biogenic amines, which correlated with these behavioural effects, were observed. Our results confirm the involvement of the dopaminergic system in MDMA-induced CPP in adolescent mice and suggest that combined consumption with or pre-exposure to cocaine increases the conditioned rewarding effects of MDMA, which may enhance the capacity of MDMA to induce dependence.

Effects of a new postnatal stress model on monoaminergic neurotransmitters in rat brains

Introduction: Stress and environmental perturbations influence postnatal brain development and may account for the high disability rates of preterm survivors following intensive care treatment. This study aims to investigate the impact of early environmental factors on the monoaminergic neurotransmitter system in the developing rat brain by using an innovative neonatal stress model. Materials and methods: After birth, in the experimental groups newborn rats were separated from their mothers and exposed to different stressful stimuli four times a day on day P0 to P6 for 10min each. To mimic intensive care treatment, the stress protocol applied environmental factors like bright light, noise, and low temperature alternating with pain and handling stress at day- and night-time in a varying sequence. The non-stressed control mothers and litters were left completely undisturbed until sacrificing on day P7 or P20. Results: Brains of stressed animals revealed significantly higher levels of norepinephrine (NE) and dopamine (DA) as determined by HPLC-ED and electrochemical detection at day P7 as compared to controls. When returned to their mothers’ undisturbed care, juvenile rats at day P20 still showed higher (yet statistically not significant) concentrations of NE and DA in brain. The stressed animals gained less weight with significantly lower body weights at day P7 compared to controls. Their mothers developed various forms of stressed behaviour. Conclusions: A novel animal model for postnatal intensive care stress was established leading to changes in brain monoamine levels of newborn rats, while undisturbed maternal care seems to moderate the stress effects subsequently.

Changes in brain monoamine levels in neonatal rats exposed to bisphenol A at low doses

To examine whether exposure to bisphenol A (BPA) at low levels affect brain function, monoamine concentrations in hippocampus, striatum and brain stem, were investigated in neonatal male rats injected intracranially with BPA at 0–10 μg kg −1. Significant increases of serotonin (5-HT) in hippocampus, 5-HIAA and 5-HIAA/5-HT in brain stem, dopamine (DA) and DOPAC in striatum were observed at 28 d after the injection on postnatal day 2. At 7 d after the injection, increases in 5-HT and norepinephrine (NE) and decreases in DOPAC and 5-HIAA were observed in hippocampus. To investigate the degradation of BPA in brain, we also measured BPA concentrations of whole neonatal rat brain. Free BPA disappeared from brain tissues within 5 h, even when the highest dose (1000 μg kg −1) was injected. The present results suggest that BPA exposure at lower doses than environmentally relevant levels may have a great impact on monoamine levels in neonatal brain over 28 d after its disappearance.

Experimental manipulations blunt time-induced changes in brain monoamine levels and completely reverse stress, but not Pb+/−stress-related modifications to these trajectories

This study sought to further understand how environmental conditions influence the outcomes of early developmental insults. It compared changes in monoamine levels in frontal cortex, nucleus accumbens and striatum of male and female Long-Evans rat offspring subjected to maternal Pb exposure (0, 50 or 150 ppm in drinking water from 2 months pre-breeding until pup weaning)+/−prenatal (PS) (restraint on GD16-17) or PS + offspring stress (OS; three variable stress challenges to young adults) determined at 2 months of age and at 6 months of age in littermates subsequently exposed either to experimental manipulations (EM: daily handling and performance on an operant fixed interval (FI) schedule of food reward), or to no experience (NEM; time alone). Time alone (NEM conditions), even in normal (control) animals, modified the trajectory of neurochemical changes between 2 and 6 months across brain regions and monoamines. EM significantly modified the NEM trajectories, and except NE and striatal DA, which increased, blunted the changes in monoamine levels that occurred over time alone. Pb+/−stress modified the trajectory of monoamine changes in both EM and NEM conditions, but these predominated under NEM conditions. Stress-associated modifications, occurring mainly with NEM OS groups, were fully reversed by EM procedures, while reversals of Pb+/−stress-associated modifications occurred primarily in nucleus accumbens, a region critical to mediation of FI response rates. These results extend the known environmental conditions that modify developmental Pb+/−stress insults, which is critical to ultimately understanding whether early insults lead to adaptive or maladaptive behavior and to devising behavioral therapeutic strategies. That time alone and a set of EM conditions typically used as outcome measures in intervention studies can themselves invoke neurochemical changes, moreover, has significant implications for experimental design of such studies.

Antidepressant-like behavioral and neurochemical effects of the citrus-associated chemical apigenin

Apigenin is one type of bioflavonoid widely found in citrus fruits, which possesses a variety of pharmacological actions on the central nervous system. A previous study showed that acute intraperitoneal administration of apigenin had antidepressant-like effects in the forced swimming test (FST) in ddY mice. To better understand its pharmacological activity, we investigated the behavioral effects of chronic oral apigenin treatment in the FST in male ICR mice and male Wistar rats exposed to chronic mild stress (CMS). The effects of apigenin on central monoaminergic neurotransmitter systems, the hypothalamic–pituitary–adrenal (HPA) axis and platelet adenylyl cyclase activity were simultaneously examined in the CMS rats. Apigenin reduced immobility time in the mouse FST and reversed CMS-induced decrease in sucrose intake of rats. Apigenin also attenuated CMS-induced alterations in serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA) levels and 5-HIAA/5-HT ratio in distinct rat brain regions. Moreover, apigenin reversed CMS-induced elevation in serum corticosterone concentrations and reduction in platelet adenylyl cyclase activity in rats. These results suggest that the antidepressant-like actions of oral apigenin treatment could be related to a combination of multiple biochemical effects, and might help to elucidate its mechanisms of action that are involved in normalization of stress-induced changes in brain monoamine levels, the HPA axis, and the platelet adenylyl cyclase activity.

A history of human‐like dieting alters serotonergic control of feeding and neurochemical balance in a rat model of binge‐eating

This study replicated a model of stress-induced binge-eating in rats with a history of caloric restriction (HCR), tested their response to SSRI (fluoxetine) treatment, and explored changes in brain monoamine levels. Young female rats with no-HCR/no-Stress, no-HCR/Stress, HCR/no-Stress, and HCR+Stress (binge-eating) were treated with fluoxetine. Post-mortem levels of serotonin, dopamine, and metabolites were assessed from brain regions key to feeding and reward. A 3 mg/kg dose of fluoxetine without effect in the no-HCR groups suppressed intake of HCR groups, normalizing the binge-eating of HCR/Stress rats. No differences in monoamines were detected in the hypothalamus or tegmentum but a strong positive relationship between accumbens serotonin and dopamine turnover in no-HCR rats was absent in rats with HCR. Despite lack of hunger, a history of human-like dieting alters serotonin function in ways suggesting consequences not only to feeding but also control of reward and mood that are dependent on dopamine/serotonin interactions.

Guest Editorial: Autism and the Environment

Guest Editorial: Autism and the Environment

The effects of valproate in brain monoamines of juvenile rats after stress

Mitsikostas Dimos, Anastasia sfikakis, Zetta Papadopoulou-Daifoti and Dionisios Varonos. The Effects of Valproate in Brain Monoamines of Juvenile Rats after Stress. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1993, 17(2): 295–310. 1. 1. Clinical data suggest that valproate (VPA) may be useful in prophylaxis of affective disorders, which show disturbances of the serotoninergic system. On the other hand, chronic stress has an adverce effect on affective disorders, those with disturbances of the serotonergic system, especially. 2. 2.In order to study the effects of VPA on brain monoamines and acute stress, 200 mgr VPA /Kgr was administered intraperitoneal (ip) to juvenile male rats; the control group was treated with NaCL 0.9% ip. After 30 min, all animals were evoked on predictable neurogenic or systemic stress (30 min foot shock, or 15 min ether stress, respectively), and 48 hours later, VPA or NaCL were administered ip again; 30 min afterwards, the rats were decapitated. Rats without stress were also sacrificed 30 min after VPA or NaCL administration. 3. 3. Measurements of brain monoamines noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT). and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxy- indoleacetic acid (5-HIAA), were done in Frontal Cortex (FC), Hypothalamus (HY) and Striatum (S), by High Performance Liquid Chromatography (HPLC). 4. 4. Compared with the control stress group the level of 5-HIAA in the FC was significantly increased (P<0.01) in VPA stress rats; in the HY and in S the increase of 5-HIAA was not significant. No remarkable differences were observed in NA, DA, 5-HT and DOPAC concentrations, in any of the brain regions. No changes in brain monoamine levels were found in non stress rats, either. 5. 5. The augmentation of 5-HIAA level after VPA administration and after stress, in correlation with the decrease of 5-HIAA that is observed in depression, support the hypothesis that VPA may be effective in affective disorders by influencing the serotoninergic system.

The Response to Acoustic Stimulation and the Changes in Brain Amine Levels after Repeated Administration of .BETA.-Phenylethylamine in Rats.

Reverse tolerance to stereotyped behavior was induced after repeated administration of beta-phenylethylamine (PEA) (50 mg/kg, i.p., daily for 10 days) in rats. The reverse tolerance was maintained for at least 4 weeks after the last administration. We studied the effects of acoustic stimulation on locomotor activity 2 days and 4 weeks after withdrawal from PEA and measured the changes in brain monoamine levels 4 weeks after the withdrawal. Locomotor activity during acoustic stimulation was increased in the saline treated group, and this response was unaffected after repeated PEA treatment. Four weeks after withdrawal, significant increases in noradrenaline levels in the cerebral cortex and decreases in 5-hydroxytryptamine levels in the hypothalamus were found. The effects of acoustic stimulation on locomotor activity and the changes in brain monoamine levels were different from those of methamphetamine treatment obtained in our previous study. In conclusion, it may be suggested that the response to acoustic stimulation after repeated PEA administration in rats cannot be a model for abnormal responsiveness to environmental stimulation that is observed in chronic paranoid schizophrenics.

Changes in brain monoamine levels and monoamine oxidase activity in the catfish,Clarias batrachus, during chronic treatments with mercurials

In mammals, the central nervous system is the primary target for CH{sub 3}Hg poisoning which is clinically known as Minamata disease. Hg is a widely recognized neurotoxin and has been reported to impair brain monoamine neurotransmitter metabolism. Reports on effects of Hg on brain monoamine activity in fishes are scarce. In the present study, therefore, changes in the brain monoamine levels and the degradation enzyme, monoamine oxidase (MAO), are described in the catfish, Clarias batrachus, exposed to sublethal concentrations of mercuric chloride (HgCl{sub 2}-inorganic Hg), methylmercuric chloride (CH{sub 3}HgCl-organic Hg), and a commercial mercurial fungicide formulation, emisan 6 (methoxyethyl Hg-organic Hg) for 45, 90 and 180 d during gonadal recrudescence. These intervals correspond to late preparatory, prespawning and spawning phases, respectively, of the annual reproductive cycle of the catfish.

Changes in brain monoamine levels of rats during cholecystokinin octapeptide-induced suppression of feeding

Cholecystokinin octapeptide (CCK-8) in doses of 5 or 10 micrograms/kg was injected intraperitoneally to 24 hr food-deprived rats before a 30 min feeding period, and the dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT) contents of the hypothalamus, mesencephalon, amygdala, hippocampus and striatum were measured thereafter. The experimental procedure (deprivation + food intake) alone could induce changes in the brain monoamine contents of saline-treated animals as compared to the nondeprived control group. The most striking effect was observed in the hypothalamus, in which the contents of all three monoamines decreased. In the deprived control group there was a significant positive correlation calculated by linear regression analysis between the amount of food eaten and the DA contents of the amygdala. Injection of CCK-8 before food intake testing decreased the DA contents of the hypothalamus. In the CCK-8-treated animals the correlation between food intake and amygdaloid DA contents disappeared. The CCK-8 treatment specifically gave rise to a significant positive correlation between the amount of food eaten and the NE content of the hypothalamus; such a relation could not be observed in the saline-treated group. The hypothalamic NE contents altered in parallel with the effectiveness of both doses of CCK-8 in inhibiting food intake. The results indicate the importance of the hypothalamic NE system in the food intake-suppressing effect of CCK-8.

Peripheral noradrenaline and adrenergic transmission in the rat.

Peripheral noradrenaline and adrenergic transmission in the rat.