Significant Increase In Dopamine Research Articles

Garcina Kola neuroprotective effects on the prefrontal cortex cyto-architecture of MDMA-induced neuroinflammation in male Wistar rats model

BackgroundThe stimulant, empathogenic, euphoric, and hallucinogenic properties of 3,4-methylenedioxymethamphetamine (MDMA), also known as 'Ecstasy,' make it a popular drug among teenagers. These effects are thought to be caused by significant increases in dopamine, serotonin, and glutamate neurotransmission. However, little is known about Garcinia kola extract's (GKE) neuroprotective activities against MDMA-induced neurotoxicity. Thus, the purpose of this study was to investigate GKE's neuroprotective activities against MDMA-induced neurotoxicity in rat models. MethodSixty (60) healthy adult male Wistar rats (120–150 g) were randomly divided into six ten-animal groups (A, B, C, D, E, and F). Group A served as the control, while groups B and C were given 100 mg/kg and 200 mg/kg (low and high) daily doses of GKE for 21 days, respectively. Group D was given a 20 mg/kg intermittent dose of MDMA, while groups E and F were given 100 mg/kg and 200 mg/kg (low and high) daily doses of GKE along with 20 mg/kg intermittent doses of MDMA for 21 days. 24 h after the last administration, the rats were sacrificed. Five rats from each group were anesthetized with a diether and perfused intracardially, after which the brains were excised and fixed in 10% neutral buffered formalin for histology and immunohistochemistry. Graph Pad Prism5 was used for the statistical analysis, which included one-way analysis of variance (ANOVA). The number of lines crossed increased significantly in MDMA-treated rats, as did the frequency of rearing and the number of lines crossed. The increase in grooming frequency observed in conjunction with a slight decrease in the number of center square entries and defecation was not statistically significant. Interestingly, dopamine, serotonin, and glutamate levels were slightly elevated in MDMA-induced psychostimulant animals, correlating with anxiolytic (animal anxiety reduction) activity. Similarly, an increase in the expression of G6PDH and Cytochrome c-oxidase was observed, indicating that MDMA has the ability to upregulate mitochondrial metabolism, which accounts for the release of more energy. As a result of MDMA treatment, histological and GFAP results revealed neuronal degeneration and astrogliosis/glia scar formation, respectively. ConclusionThis finding demonstrates MDMA's neurotoxic damage to neurons in the prefrontal cortex, its ability to cause behavioural deficits, and how GKE administration was able to slow down MDMA's neurotoxic damage and behavioural deficits.

Acute titanium dioxide nanoparticles exposure impaired spatial cognitive performance through neurotoxic and oxidative mechanisms in Wistar rats

Context Titanium dioxide nanoparticles (TiO2-NPs) are used in many commercial products. However, their effects on human and animal organism remained to be clarified. Objective The present study aimed to investigate the effects of TiO2-NPs on the behavioural performance, monoamine neurotransmitters and oxidative stress in the rat brain. Material and methods Rats were injected intravenously with a single dose of TiO2-NPs (20 mg/kg body weight) and were subjected to cognitive and emotional tests using Morris water maze and elevated plus maze. Results Cognitive capacity as well as the emotional reactivity were significantly disrupted, in TiO2-NPs-administered rats compared to control group. These behavioural effects were correlated with changes in brain neurotransmitter contents reflected by a significant increase in dopamine and a decrease in serotonin levels. TiO2-NPs also induced oxidative stress in the brain manifested by increased levels of H2O2 and malondialdehyde, associated with antioxidant enzymes activities disturbance, in particular, superoxide dismutase and catalase activities. Moreover, TiO2-NPs administration caused histological damages in the brain tissue with abundant lymphocytic clusters, capillary dilations, vascular congestion and oedema. Conclusions Acute intravenous injection of TiO2-NPs impaired behaviour performances through brain biochemical and structural changes and precautions should be taken to their usage in food additive and medical applications.

Glyphosate targets fish monoaminergic systems leading to oxidative stress and anxiety

Glyphosate is the active ingredient of some of the most highly produced and used herbicides worldwide. The intensive applications of glyphosate-based herbicides and its half-life in water lead to its presence in many aquatic ecosystems. Whereas recent studies have reported neurotoxic effects of glyphosate including autism-related effects, most of them used extremely high (mg/L to g/L) concentrations, so it is still unclear if chronic, low environmentally relevant concentrations of this compound (ng/L to μg/L) can induce neurotoxicity. In this study we analyzed the neurotoxicity of glyphosate in adult zebrafish after waterborne exposure to environmentally relevant concentrations (0.3 and 3 μg/L) for two weeks. Our data showed that exposed fish presented a significant impairment of exploratory and social behaviors consistent with increased anxiety. The anterior brain of the exposed fish presented a significant increase in dopamine and serotonin levels, as well as in the DOPAC/dopamine and homovanillic acid/dopamine turnover ratios. Moreover, the expression of genes involved in the dopaminergic system, as th1, th2, comtb, and scl6a3 was downregulated. Finally, the brain of exposed fish presented a significant increase in the catalase and superoxide dismutase activities, with a concomitant decrease of glutathione stores. These changes in the antioxidant defense system are consistent with the observed increase in oxidative stress, reflected by the increase in the levels of lipid peroxidation in the brain. The presented results show that current glyphosate concentrations commonly found in many aquatic ecosystems may have detrimental consequences on fish survival by decreasing exploration of the environment or altering social interactions. Furthermore, as zebrafish is also a vertebrate model widely used in human neurobehavioral studies, these results are relevant not only for environmental risk assessment, but also for understanding the risk of chronic low-dose exposures on human health.

The interactive effects of ketamine and ethanol on dopamine expression in the ventral tegmental area of rats

BackgroundA number of studies have demonstrated the significant and rapid antidepressant effects of ketamine, which is also known as a neurotoxic and illicit drug. Ketamine and alcohol are increasingly used together in clubs by teenagers and young adults. Previous studies have proven that chronic ketamine consumption induces a delayed and persistent activation of the dopamine (DA) system. However, the rewarding properties of recreational ketamine abuse remain unclear, and the underlying mechanisms of the effects on the DA system after administration of ketamine with ethanol are yet to be explored.MethodsHere, we evaluated the effects of two different doses of ketamine (30 mg/kg and 60 mg/kg) with and without ethanol (0.3156 g/kg) on DA concentration in the rat’s ventral tegmental area (VTA), a vital region in the reward and motivation system. We explored the effects of the combined drug treatment on the expression profiling of the DA metabolism genes, tyrosine hydroxylase, dopa decarboxylase, vesicular monoamine transporter 2, and synaptosomal-associated protein 25, as well as protein expression level of brain-derived neurotrophic factor in the rat’s VTA.ResultsWe found that administration of ketamine with ethanol led to a significant increase of DA in the VTA associated with differential regulation of mRNA levels of the four DA metabolism genes and protein levels of brain-derived neurotrophic factor. Moreover, the rewarding properties of coadministration of ketamine and ethanol were related to dopaminergic neuron activation in the VTA.ConclusionThese results indicated the possibility that combined drug treatment might positively affect the mesencephalic DA reward system.

Effect of Vaccinium macrocarpon on MK-801-induced psychosis in mice.

OBJECTIVES:This study was aimed to investigate the effect of aqueous cranberry extract (ACE) on MK-801-induced psychosis in mice.MATERIALS AND METHODS:MK-801-treated mice were administered ACE (1 and 2 g/kg, p.o.) for 14 days. Various behavioral parameters and neurochemical estimations such as dopamine (DA), 5-hydroxytryptamine (5-HT), norepinephrine (NE), gamma-aminobutyric acid (GABA), glutamate, and glycine as well as markers of oxidative stress such as nitrite levels were measured.RESULTS:Psychosis-induced mice showed a significant elevation of immobility time in forced swim test, locomotor activity, and reduction in time of permanency in rota-rod test, escape latency time in Cook's pole test while treatment with ACE showed a significant alteration in above-mentioned behavioral parameters in MK-801-induced psychosis. Moreover, MK-801-induced psychosis in the mice showed a significant increase in DA, 5-HT, and NA levels and decrease in GABA, glutamate, and glycine levels in the brain. In contrast, treatment with ACE at both doses remarkably altered the neurochemical parameters. In addition, ACE-treated mice showed a substantial reduction in acetylcholinesterase, D-amino acid oxidase enzyme activity, and nitrite levels which were elevated by the administration of MK-801.CONCLUSIONS:Treatment with ACE once for 14 days (1 and 2 g/kg) significantly ameliorated the behavioral symptoms in experimentally induced psychosis by virtue of neuromodulation and decreased oxidative stress.

Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: A preliminary investigation.

Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR). Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for 7 days, followed by 7 days washout. In vivo microdialysis was carried out prior to, during and following the NOR task. Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial ( p < 0.01). scPCP produced a significant deficit in NOR ( p < 0.05 vs. control) and no PFC dopamine increase was observed. These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology.

Indices of the antioxidant system and dopamine in blood plasma in the dynamics of microwave resonance therapy in patients with alcoholism

To study effects of microwave resonance therapy (MWRT) on the level of dopamine and some indices of the antioxidant system of blood plasma in patients with alcohol dependence. Dopamine, reduced glutathione, activities of catalase and superoxidismutase (SOD) were measured in blood plasma of alcoholic patients (50 men) before and after therapy. Plasma of 25 physically and mentally healthy men matched for age was used as control. In alcoholic patients in withdrawal state, the significant increase in dopamine (p=0.03), activity of catalase and SOD (p<0.05) as well as a decrease in reduced glutathione (p<0.01) in blood plasma in comparison with controls were found. The level of dopamine decreased significantly as after conventional therapy, as well after the therapy with addition of MWRT. After MWRT, the level of glutathione in blood plasma increased significantly and activities of catalase and SOD decreased practically up to the control level while after conventional therapy (without MWRT), the indices of the antioxidant system did not change significantly. The inclusion of MWRT in complex treatment of patients with alcoholism contributes to the normalization of the activity of catalase and SOD and increases the level of reduced glutathione, but has no significant effect on blood plasma dopamine level.

Symbiotic effect of sodium selenite and vitamin E against lithium carbonate induced brain toxicity in male rats

Lithium drugs have mainly used in the treatment of psychiatric diseases, therefore many side effects resulting from this metal after used for cure. Sothat in the current study we have to determine the effect of lithium carbonate (Li2CO3) after administration orally for six and eight weeks on the neurotransmitters (dopamine, serotonin) and his to pathological changes in brain tissues in the male rats. Fifty adult male rats weighting 200-250 gm were divided into four groups (10 rats in each group). group one received distilled water and kept as negative control. Group tow received lithium carbonate at dose 4 mg/kg only, group three received lithium carbonate at dose 8 mg/kg only also kept as negative control, group four received lithium carbonate at dose 4 mg/kg with antioxidant solution contain sodium selenite at dose of 2.4 mg/ml and vitamin E at dose of 60 mg/ml daily and group five received lithium carbonate at dose 8 mg/kg with antioxidant solution containing sodium selenite at dose of 2.4 mg/ml and vitamin E at dose of 60 mg/ml daily. Rats after anaesthetized by the mixture of xylazine and ketamine for collocation of serum for biochemical and brain for his to pathological analysis. The results appeared a significant decrease in dopamine and a significant increase of serotonin in the groups of rats treated with lithium carbonate only and intracellular edema, perivascular edema also neurophagia in brain of Li2CO3 treated rats. Co-treatment of rats with vitamin E and sodium selenite results showed a significant increase in dopamine and significant decrease in serotonin with normal tissue structure of the brain. Finally, the results in the current study demonstrated the protective effect of sodium selenite and vitamin E against toxicity by using lithium carbonate.

Anti-depressant-like effect of curculigoside isolated from &lt;i&gt;Curculigo orchioides&lt;/i&gt; Gaertn root

Purpose: To investigate the anti-depressant-like activity of curculigoside from Curculigo orchioides Gaertn and its underlying mechanism(s). Methods: Antidepressant-like activity was determined in mice through forced swimming test (FST), tail suspending test (TST), and open field test (OFT). Mechanism of action was investigated by measuring levels of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) in chronic mild stress (CMS) rats using high-performance liquid chromatography-electron capture detector (HPLC-ECD). Western blotting was used to investigate the effect of curculigoside on the expression of brain-derived neurotrophic factor (BDNF) protein in rats. Results: In FST and TST, treatment of mice with curculigoside (10, 20, 40 mg/kg, p.o.) significantly reduced immobility time, which was, however, unaffected by locomotor activity when assessed in the OFT. The treatment led to significant increases in DA, NE and 5-HT, and up-regulation of BDNF protein expression in the hippocampus of the CMS rats. Conclusion: These results demonstrate that curculigoside exerts significant anti-depressant-like activity on mice, the mechanism of which involves increase in the levels of DA, NE, 5-HT, and up-regulation of BDNF expression. Thus, curculigoside can be considered a potential drug candidate for the treatment of depressive disorders. Keywords: Curculigo orchioides Gaertn, Curculigoside, Antidepressant-like activity, Behavioral studies

Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics

BackgroundStriatal dopamine (DA) has been implicated in alcohol use disorders, but it is still unclear whether or not alcohol can induce dopamine release in social drinkers. Furthermore, no data exist on dopamine responses to alcohol in dependent drinkers. We sought to characterize the DA responses to alcohol intoxication in moderately large samples of social drinkers (SD) and nontreatment-seeking alcoholics (NTS). MethodsTwenty-four SD and twenty-one NTS received two [11C]raclopride (RAC) PET scans; one at rest, and one during an intravenous alcohol infusion, with a prescribed ascent to a target breath alcohol concentration (BrAC), at which it was then “clamped.” The alcohol clamp was started 5min after scan start, with a linear increase in BrAC over 15min to the target of 80mg%, the legal threshold for intoxication. Target BrAC was maintained for 30min. Voxel-wise binding potential (BPND) was estimated with MRTM2. ResultsIV EtOH induced significant increases in DA in the right ventral striatum in NTS, but not SD. No decreases in DA were observed in either group. ConclusionsAlcohol intoxication results in distinct anatomic profiles of DA responses in SD and NTS, suggesting that in NTS, the striatal DA system may process effects of alcohol intoxication differently than in SD.

Therapeutic role of quercetin on oxidative damage induced by acrylamide in rat brain

Context Quercetin (QE), a bioflavonoid present abundantly in fruits and vegetables, has been reported to possess antioxidant properties. Acrylamide (ACR) is formed in foods during cooking and is known to be neurotoxic.Objective The present study was designed to evaluate the protective effect of QE against neurotoxicity induced by ACR.Materials and methods Four groups of Wistar rats consisting of six rats each: (i) control group; (ii) acrylamide treated group (50 mg/kg body weight as single dose); (iii) quercetin group: rats were treated intraperitoneally (i.p.) with QE (10 mg/kg body weight alone every day for 5 d); (iv) quercetin + acrylamide group: quercetin (10 mg/kg bw) was given i.p. every day for 5 d followed by acrylamide i.p. injection (50 mg/kg bw) on fifth day (single dose). Rats were killed after 48 h.Results Administration of ACR (50 mg/kg bw) in Wistar rats resulted in significant increase of dopamine, interferon-γ and 8-hydroxyguanosine with concomitant decrease of serotonin (p < 0.001) in the rat brain. Treatment of rats with QE intraperitonealy (10 mg/kg body weight) before ACR assault resulted in the diminution of ACR-mediated neurotoxicity as evident from decreased levels of dopamine, interferon-γ (p < 0.001) and 8-hydroxyguanosine with concomitant restoration of serotonin levels (p < 0.001).Discussion and conclusion On the basis of the above results, the present study suggests that quercetin may be a potential therapeutic agent for restoration of oxidative damage to neurons.

Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model of Parkinson's disease

BackgroundTo circumvent the challenges associated with delivering large compounds directly to the brain for the treatment of Parkinson's disease (PD), non-invasive procedures utilizing smaller molecules with protective and/or restorative actions on dopaminergic neurons are needed. New methodWe developed a methodology for evaluating the effects of a synthetic neuroactive peptide, DNSP-11, on the nigrostriatal system using repeated intranasal delivery in both normal and a unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of PD. ResultsNormal rats repeatedly administered varying doses of DNSP-11 intranasally for 3 weeks exhibited a significant increase in dopamine (DA) turnover in both the striatum and substantia nigra (SN) at 300μg, suggestive of a stimulative effect of the dopaminergic system. Additionally, a protective effect was observed following repeated intranasal administration in 6-OHDA lesioned rats, as suggested by: a significant decrease in d-amphetamine-induced rotation at 2 weeks; a decrease in DA turnover in the lesioned striatum; and an increased sparing of tyrosine hydroxylase (TH) positive (+) neurons in a specific sub-region of the lesioned substantia nigra pars compacta (SNpc). Finally, tracer studies showed 125I-DNSP-11 distributed diffusely throughout the brain, including the striatum and SN, as quickly as 30min after a single intranasal dose. Comparison with existing methodsThe results of bilateral intranasal administration of DNSP-11 are compared to our unilateral single infusion studies to the brain in rats. ConclusionsThese studies support that DNSP-11 can be delivered intranasally and maintain its neuroactive properties in both normal rats and in a unilateral 6-OHDA rat model of PD.

Comparative studies on behavioral neurochemical effects of N,α-diethylphenethylamine and methamphetamine in rats

One objective was to compare the psychostimulating effects of N,α-diethylphenethylamine (NADEP) with those of methamphetamine (METH) in experiments on behavioral activities of rats. Another objective was to compare concentrations of neurotransmitters dopamine (DA), serotonin (5-HT), and their metabolites such as dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in brain tissues (striatum and frontal cortex) carried out after administration of NADEP and METH in rats. The animals were treated with NADEP and METH for 6 consecutive days (5 mg/kg per day, respectively), and the scores of stereotypy were measured on the first, second, fourth, and sixth day. The increase of the stereotypy score was observed in the NADEP-treated group, but it was less than that after treatment with METH. NADEP administration (5 and 10 mg/kg) resulted in a significant increase of DA and 5-HT and a decrease of DOPAC and HVA in the striatum tissues, which were collected 1 h after administration, but the changes of the compounds were less than those after treatment with METH (5 mg/kg). Unlike the METH-treated group, the changed DA, 5-HT, DOPAC, and HVA levels of the NADEP- treated group (5 and 10 mg/kg) were soon recovered within 6 h after administration. Both NADEP and METH had no significant effect on the 5-HIAA concentrations of the brain tissues. These results suggest that NADEP has significant psychostimulatory effects, though the effects were less than those of METH. Thus, NADEP should be carefully monitored to avoid abuse as a psychoactive drug.

Ser31 tyrosine hydroxylase phosphorylation parallels differences in dopamine recovery in nigrostriatal pathway following 6‐OHDA lesion

Compensatory mechanisms in dopamine (DA) signaling have long been proposed to delay onset of locomotor symptoms during Parkinson's disease progression until ~80% loss of striatal DA occurs. Increased striatal dopamine turnover has been proposed to be a part of this compensatory response, but may occur after locomotor symptoms. Increased tyrosine hydroxylase (TH) activity has also been proposed as a mechanism, but the impact of TH protein loss upon site-specific TH phosphorylation in conjunction with the impact on DA tissue content is not known. The tissue content of DA was determined against TH protein loss in the striatum and substantia nigra (SN) following 6-hydroxydopamine lesion in the medial forebrain bundle in young Sprague-Dawley male rats. Although DA predictably decreased in both regions following 6-hydroxydopamine, there was a significant difference in DA loss between the striatum (75%) and SN (40%), despite similar TH protein loss. Paradoxically, there was a significant decrease in DA against remaining TH protein in striatum, but a significant increase in DA against remaining TH in SN. In the SN, increased DA per remaining TH protein was matched by increased ser31, but not ser40, TH phosphorylation. In striatum, both ser31 and ser40 phosphorylation decreased, reflecting decreased DA per TH. However, in control nigral and striatal tissue, only ser31 phosphorylation correlated with DA per TH protein. Combined, these results suggest that the phosphorylation of ser31 in the SN may be a mechanism to increase DA biosynthesis against TH protein loss in an in vivo model of Parkinson's disease. Properties of dopamine biosynthesis were evaluated in the 6-OHDA model of Parkinson's disease by studying the impact of tyrosine hydroxylase (TH) protein loss on its own phosphorylation and dopamine (DA) tissue content in rat nigrostriatal pathway. A dichotomous response was observed between striatum and substantia nigra in that dopamine per remaining TH decreased in striatum, but increased in substantia nigra. Phosphorylation at ser31 reflected these differences, indicating that ser31 phosphorylation may be critical to maintain dopamine with progressive TH protein loss. Drawings are from slides purchased from Motifolio (http://motifolio.com/).

Effects of sub-acute exposure to TiO2, ZnO and Al2O3 nanoparticles on oxidative stress and histological changes in mouse liver and brain

Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO2, ZnO and Al2O3 on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500 mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.

Lactation Reduces Stress-Caused Dopaminergic Activity and Enhances GABAergic Activity in the Rat Medial Prefrontal Cortex

We investigated the effect of restraint on the release of dopamine, GABA and glutamate in the medial prefrontal cortex (mPFC) of lactating compared with virgin Wistar female rats; besides the expression of D1, neuropeptide Y Y2, GABA receptors and corticotropin-releasing factor (CRF). Results from microdialysis experiments showed that basal dopamine and GABA, but not glutamate, concentrations were higher in lactating rats. In virgin animals, immobilization caused significant increase in dopamine, whereas GABA was unchanged and glutamate reduced. In lactating animals, restrain significantly decreased dopamine concentrations and, in contrast to virgin animals, GABA and glutamate concentrations increased. We found a higher expression of CRF, as well as the D1 and neuropeptide Y Y2 receptors in the left mPFC of virgin stressed rats; also, only stressed lactating animals showed a significant increase in immunopositive cells to GABA in the left cingulate cortex; meanwhile, a significant decrease was measured in virgin rats after stress in the left prelimbic region. The increased inhibition of the mPFC dopamine cells during stress and the down-regulated expression of the neuropeptide Y Y2 receptor may explain the lower CRF and hyporesponse to stress measured in lactating animals. Interestingly, participation of mPFC in stress regulation seems to be lateralized.

Orexigenic effects of endomorphin-2 (EM-2) related to decreased CRH gene expression and increased dopamine and norepinephrine activity in the hypothalamus

Endomorphin-1 (EM-1) and endomorphin-2 (EM-2) are opioid peptides which are selective partial agonists of μ-opioid receptor. We studied the effects of EM-2 injected into the arcuate nucleus (ARC) of the hypothalamus on feeding behavior and gene expression of orexigenic [agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A] and anorexigenic [cocaine and amphetamine-regulated transcript (CART), corticotrophin releasing hormone (CRH) and proopiomelanocortin (POMC)] peptides in male Wistar rats fed a standard laboratory diet. Furthermore, we evaluated the effects of EM-2 on dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) steady state concentrations, in the hypothalamus. 64 rats (16 for each group of treatment) were injected into the ARC, at 9.00am, with either vehicle or EM-2 (0.50–0.75μmol/kg) or EM-2 (0.50μmol/kg) plus β-funaltrexamine (0.20μmol/kg). Food intake was recorded through 24h following injection, and hypothalamic DA, NE, 5-HT levels and neuropeptide gene expression were evaluated 24h after EM-2 administration. Compared to vehicle, EM-2 significantly increased food intake, throughout 24h post-injection. Furthermore, EM-2 treatment led to a significant increase of DA and NE concentrations and a decrease of CRH mRNA levels. On the other hand, β-funaltrexamine administration reverted both feeding stimulatory and neuromodulatory effects induced by EM-2. We can conclude that the orexigenic effect of μ-opioid receptor activation by EM-2 could be related to both inhibition of CRH and stimulation of dopamine and norepinephrine levels, in the hypothalamus.

Antidepressants and mood stabilizers effects on histone deacetylase expression in C57BL/6 mice: Brain region specific changes

To determine whether treatment with various antidepressants or mood stabilizers leads to region-specific changes, we investigated the effects of their subchronic (14 days of intraperitoneal injection) administration on the tissue concentration of monoamines, dopamine, serotonin, and norepinephrine, and the protein expression of acetylated histone H3 (AcH3) and histone deacetylases (HDACs) in the mouse striatum (ST), nucleus accumbens (Acb), hippocampus (Hip), cingulate cortex (Cg), and amygdala (Amy). Subchronic administration with the antidepressants (S)-citalopram oxalate (ECM), duloxetine hydrochloride (DLX), and mirtazapine (MIR) commonly induced significant increases in dopamine and serotonin levels in the ST and Cg. By contrast, no common profiles for dopamine, serotonin, or norepinephrine were identified in the Acb, Hip, or Amy. Treatment with sodium valproate (VPA), lithium chloride (Li), lamotrigine (LTG), levetiracetam (LTM), olanzapine (OLZ), clozapine (CLZ), clomipramine (CLM), ECM, and DLX induced significant increases in AcH3 expression in the Acb, while treatment with CLM, ECM, DLX, MIR, carbamazepine (CBZ), LTG, LTM, OLZ, or CLZ induced significant increases in HDAC2 and HDAC3 in the ST. CLM, MIR, VPA, CBZ, LTG, LTM, OLZ, or CLZ induced significant increases in HDAC3 in the Cg, and ECM, DLX, MIR, VPA, CBZ, LTG, LTM, or OLZ resulted in significant increases in HDAC5 in the Amy. Collectively, the changes of monoamine content were restricted for mood stabilizer effects, but increased expression of HDAC2, HDAC3, or HDAC5 in the ST, Cg, or Amy was often found, supporting the possibility that antidepressant-like effects involve epigenetic modifications associated with changes in HDAC expression.

English

Two experiments were conducted to compare the effects of feeding blends of wheat grains naturally contaminated with deoxynivalenol (DON) and maize products contaminated with&nbsp;Fusarium&nbsp;(FUM) mycotoxins on brain regional concentration of&nbsp;&nbsp;brain dopamine (DA), norepinephrine (NE) and serotonin (5-HT)&nbsp; in hippocampus, mid brain, cortex, striatum, pons and medulla and cerebellum of male albino mice. Daily feeding of wheat or maize grains contaminated with deoxynivalenol&nbsp; in a dose level (803 &micro;g/kg) or&nbsp; fumonisin&nbsp; in a dose level (1330 ppb)&nbsp; for six weeks caused highly significant&nbsp; increase in dopamine (DA), norepinephrine (NE) and serotonin (5-HT ) contents, in most of the studied mice brain areas. When all the studied brain areas were compared, it can be concluded that hypothalamus-dopamine concentration was more sensitive towards the studied toxicants. On the other hand, except for norepinephrine in pons and medulla oblongata, there was a significant increase in epinipherine and serotonin levels at all the studied brain areas.&nbsp; Maximal concentration, however, was attained in the cortex for both neurotransmitters. Additionally, rearing behavior was found to increase following feed intake of the test feed and deoxynivalenol was found to modulate more behavioral disturbances as compared with fuminisin.&nbsp; The data recorded also showed a highly significant increase in the aggressive and locomotor behavior of the intoxicated albino mice. &nbsp; Key words:&nbsp;Deoxynivalenol, fumonisin, brain areas, monoamines.

Interactions of dopamine (DA) D2‐like receptor availability and DA transporters (DAT) on cocaine self‐administration in female cynomolgus monkeys

Using PET imaging, we recently reported that female monkeys who become dominant showed a significant increase in dopamine (DA) D2‐like receptor availability compared to subordinate animals who showed significant decreases in DA transporter (DAT) availability (Nader et al. 2012). In contrast to males, it appears that higher D2‐like availability was associated with greater vulnerability to cocaine reinforcement. However, it is possible that DAT availability was the more important vulnerability trait. The goal of this study was to further examine the role of D2‐like receptor and DAT availability on cocaine self‐administration (SA) in female cynomolgus monkeys (n=10). Individually housed female monkeys were scanned twice, once with the D2‐like receptor ligand [11C]raclopride and once with the DAT ligand [18F]FECNT. All monkeys were trained to respond under a multiple fixed‐interval 3‐min schedule of food and cocaine reinforcement. Food was available in components 1 and 3 and drug (or saline) in components 2 and 4. Although still preliminary, there appears to be no relationship between food‐maintained responding and DAT availability. Cocaine will be made available for SA and responding will be correlated with D2‐like and DAT availability. These studies will provide important information related to DA receptor function and vulnerability in a female monkey model of cocaine abuse. DA017763