Effects Of Long-term Administration Research Articles

Methyl- rich diet ameliorates lupus-like disease in MRL/lpr mice

Genetic susceptibility is necessary but not sufficient for systemic lupus erythematosus (SLE) to appear indicating that environmental factors are also key components in the disease onset. Aberrant DNA methylation profile positively correlates with the development of lupus-like disease in MRL/lpr mice. In the present study, we evaluate the effect of long term administration of methyl-rich diet in MRL mice. The results showed that supplemented diet decreased the levels of proteinuria and of anti-dsDNA antibodies and modulated cytokine profiles. Limited kidney failure and prevented development of skin lesions in MRL/lpr mice were another positive effects of the high-dose methyl diet. These data suggest that it is possible to modulate the disease course by altering the amount of particular dietary micronutrients and that nutrition-mediated changes in DNA methylation may have potential clinical relevance.

ПОКАЗАТЕЛИ ФОНДА СВОБОДНЫХ АМИНОКИСЛОТ И ИХ ДЕРИВАТОВ В ПЛАЗМЕ КРОВИ И ПЕЧЕНИ КРЫС ПРИ ВВЕДЕНИИ ТИОАЦЕТАМИДА

Summary. Aim. To evaluate the effect of long-term administration of thioacetamide (TAA) on the levels of free amino acids and related compounds in the blood plasma and liver of rats. Material and methods. The animals were given TAA at a dose of 200 mg/kg every other day, 4 and 12 weeks. In the blood plasma and liver of rats levels of free amino acids (AA) and low molecular weight SH-containing compounds were determined by high performance liquid chromatography. Results. Long-term administration of TAA caused hyperaminoacidemia. In the rat liver, after 4 weeks of TAA administration, the content of sulfur-containing compounds decreased, the content of proteinogenic AAs (including aromatic and branched-chain AAs) increased, and after 12 weeks the concentration of all the studied compounds increased. The levels of α-aminobutyric acid, serine, cysteate, homocysteate in the rat liver, and serine, glycine, taurine, glutathione in blood plasma, made the main endowment to the overall discrimination of the experimental groups. Conclusions. Thioacetamide damage causes amino acid imbalance, the severity of which depends on the degree of cytolysis in the liver, dysfunction of the γ-glutamyl cycle, which is confirmed by an increase in the levels of key metabolites of these reactions both in the liver and in the blood plasma.

Effect of long-term administration of clonazepam, carbamazepine, and valproate on cognitive, psychological, and personality changes in adult epilepsy: a case\u2013control study

BackgroundEpilepsy can be treated with antiepileptic drugs (AEDs) which may have psychiatric and behavioral side effects. Additionally, the availability of new AEDs has increased, and our understanding of variability to combinations of several AEDs has evolved. Based on the treatment outcomes of carbamazepine, valproate, and clonazepam, this study aims to compare the cognitive function, personality, and psychological issues associated with these drugs and evaluate seizure-related factors related to them. Only 139 participants were included. Clonazepam was used as an add-on antiepileptic drug. Participants were categorized into five groups: group 1, carbamazepine; group 2, valproate; group 3, carbamazepine and clonazepam; group 4, valproate and clonazepam; and group 5, epileptic patients without AED. All participants were assessed using the Wechsler Adult Intelligence Scale (WAIS), Structured Interview for the Five-Factor Personality Model (SIFFM), Hamilton Anxiety and Depression Rating Scale, and Minnesota Multiphasic Personality Inventory-2 (MMPI-2).ResultsIn the WAIS, group 1 had the worst mean of verbal intelligence quotient (IQ). Moreover, group 3 was more vulnerable in symptomatic response in all subscales of MMPI-2 except the masculinity–femininity subscale and a high percentage in moderate severity of anxiety and depression in the Hamilton scales.ConclusionsThe use of clonazepam and carbamazepine might increase the incidence of behavioral problems especially increased severity of anxiety and depression and decreased performance IQ compared with either clonazepam or carbamazepine alone. Moreover, patients with carbamazepine treatment might have more personality changes and lowered verbal IQ than others.

A Study on the Effects of Some Medicinal Plants, Specifically Ashwagandha (Withania somnifera), on Activity, Autonomic Reactivity, Escape/Avoidance Learning and Response Rate in Albino Rats

The present study investigated the effects of long term administration of crude powder and liquid tonic forms of ashwagandha (Withania somnifera) on behaviour in albino rats. The behavioural measures included general motor activity (measured in Revolving Wheel Apparatus), autonomic reactivity (measured in Open Field Test Apparatus), response latency (measured in Two-way Shuttle Box) and response rate (measured in Skinner Box). A 3g/kg treatment of the crude powder of ashwagandha through food did not show any significant effect on any of the behavioural measures. Similar results were obtained for 2ml/kg treatment of the tonic. Another experiment was conducted to compare the effects of ashwagandha, mandukaparni (Centella asiatica), jyotishmati (Celastrus paniculatus), vacha (Acorus calamus) and shankhpushpi (Convolvulus pluricaulis). Jyotishmati treated subjects had lower general activity scores as compared to other groups. Autonomic reactivity did not differ among the various drug treated groups. Lower response latency in jyotishmati treated group indicated faster learning than in other groups. Jyotishmati and vacha treatment also resulted in better response strength as compared to the other treatments. It is concluded that the crude forms of plant medicines often used by people may not be much effective in most cases.

Persistent effects of the orexin-1 receptor antagonist SB-334867 on naloxone precipitated morphine withdrawal symptoms and nociceptive behaviors in morphine dependent rats

Aim of the study In this study, we investigated the effect of long-term administration of orexin receptor 1 (OXR1) antagonist on naloxone-precipitated morphine withdrawal symptoms and nociceptive behaviors in morphine-dependent rats. Materials and methods Wistar rats received subcutaneous (s.c.) injections of morphine (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) at an interval of 24 h for 7 days. In chronic groups, the OXR1 antagonist, SB-334867 (20 mg/kg, i.p.), or its vehicle, was injected repetitively from postnatal day 1 (PND1)-PND23 and then for the following seven days before each morphine injection. Meanwhile, in acute groups, SB-334867, or its vehicle, was administered before each morphine injection. In groups of rats that were designated for withdrawal experiments, naloxone (2.5 mg/kg, i.p.) was administered after the last injection of morphine. In the formalin-induced pain, the effect of OXR1 inhibition on the antinociceptive effects of morphine was measured by injecting formalin after the final morphine injection. Results Animals that received long-term SB-334867 administration before morphine injection demonstrated a significant reduction in chewing, defecation, diarrhea, grooming, teeth chattering, wet-dog shake, and writhing. Inhibiting OXR1 for a long time increased formalin-induced nociceptive behaviors in interphase and phase II of the formalin-induced pain. Conclusions Our results indicated that the inhibition of OXR1 significantly reduces the development of morphine dependence and behavioral signs elicited by the administration of naloxone in morphine-dependent rats. Furthermore, the prolonged blockade of OXR1 might be involved in formalin-induced nociceptive behaviors.

Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice

RationaleAmylin receptors consist of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs). The identification of amylin receptors in areas processing reward, namely laterodorsal tegmental area (LDTg), ventral tegmental area (VTA), and nucleus accumbens (NAc), has attributed them a role as reward regulators. Indeed, acute activation of amylin receptors by the amylin receptor agonist salmon calcitonin (sCT) attenuates alcohol-induced behaviours in rodents.ObjectivesThe effects of long-term administration of sCT on alcohol-related behaviours and the molecular mechanisms underlying these processes are not yet elucidated. To fill this knowledge gap, we investigated the effects of sub-chronic sCT treatment on the locomotor stimulatory responses to alcohol in mice and the molecular pathways involved.MethodsWe assessed the behavioural effects of sub-chronic sCT treatment by means of locomotor activity experiments in mice. We used western blot to identify changes of the CTR levels and ex vivo biochemical analysis to detect changes in monoamines and their metabolites.ResultsAfter discontinuation for 5 days of sCT treatment, alcohol did not induce locomotor stimulation in mice pre-treated with sCT when compared with vehicle, without altering secondary behavioural parameters of the locomotor activity experiment or the protein levels of the CTR in reward-related areas in the same set of animals. Moreover, repeated sCT treatment altered monoaminergic neurotransmission in various brain areas, including increased serotonin and decreased dopamine turnover in the VTA. Lastly, we identified a differential effect of repeated sCT and acute alcohol administration on alcohol-induced locomotion in mice, where sCT initially attenuated and later increased this alcohol response. It was further found that this treatment combination did not affect secondary behavioural parameters measured in this locomotor activity experiments.ConclusionsThese data suggest that sub-chronic sCT treatment differentially alters the ability of alcohol to cause locomotor stimulation, possibly through molecular mechanisms involving various neurotransmitter systems and not the CTR levels per se.

1125-P: Association of Plasma Volume with Body Weight and BNP after Long-Term Administration and Subsequent Withdrawal of the SGLT2 Inhibitor Tofogliflozin

SGLT2 inhibitors (SGLT2is) promote diuresis and reduce plasma volume (PV). However, the impact of long-term administration and subsequent withdrawal of SGLT2is on PV is little known. This study investigated the effect of long-term administration and then withdrawal of the SGLT2i, tofogliflozin (TOFO), on PV and explored correlations with variables in type 2 diabetes mellitus (T2DM). Analyzed were 166 T2DM patients who received TOFO for 52 weeks as initial monotherapy and underwent 2 weeks of withdrawal (week 54) in a phase-3 study. Percent change in estimated PV (%ΔePV) was calculated by the Strauss formula: {100*(pre Hb/post Hb)*[(100 - pre Ht)/(100 - post Ht)] - 100}. Baseline characteristics were: male (66%), age (mean: 58 y), HbA1c (8%), BMI (26kg/m2), BNP (12pg/mL) and eGFR (84mL/min/1.73m2). Paired t-tests analyzed differences from baseline to week 52 and from week 52 to 54. Correlation analysis was performed by Pearson’s product-moment correlation coefficients. Multivariate analysis explored predictors for %ΔePV. Body weight (BW) [mean, -3kg (-5%)*; * p<0.01 vs. baseline], ePV (-2.7%*) and ln-transformed BNP [ln-BNP: -0.1ln(pg/mL)*] had significantly decreased by week 52. %ΔBW was not significantly correlated with %ΔePV (r=-0.06) and Δln-BNP (r=0.13) while %ΔePV was significantly correlated with Δln-BNP (r=0.35). Higher baseline ln-BNP levels were independently correlated with greater reductions in %ΔePV. After 2 weeks of withdrawal, BW [+0.9kg (+1.3%)†, † p<0.001 vs. week 52], ePV (+6.5%†) and ln-BNP [+0.3ln(pg/mL) †] were significantly increased. %ΔBW was significantly correlated with %ΔePV (r=0.22) and Δln-BNP (r=0.32). Also, %ΔePV was significantly correlated with Δln-BNP (r=0.30). After long-term TOFO therapy, reduced PV might be correlated not with weight loss but with reduced BNP indicating fluid loss and baseline BNP might predict changed PV. Weight gain after TOFO withdrawal might be caused by fluid gain. Disclosure Y. Matsubayashi: None. A. Yoshida: Employee; Self; Kowa Company, Ltd. T. Nojima: Employee; Self; Kowa Company, Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd. K. Fujihara: None. K. Kaku: Advisory Panel; Self; Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc. Consultant; Self; Sanwa Kagaku Kenkyusho. Research Support; Self; Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer\u2019s disease mice

BackgroundNeuropsychiatric symptoms (NPS) such as depression, anxiety, apathy, and irritability occur in prodromal phases of clinical Alzheimer’s disease (AD), which might be an increased risk for later developing AD. Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor (SSRI) paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress.MethodsTo investigate the protective role of paroxetine in emotional abnormalities and cognitive defects during disease progress, we performed emotional behaviors of 3 months old APP/PS1 mouse following oral administration of paroxetine prophylactically starting at 1 month of age. Next, we tested the cognitive, biochemical and pathological, effects of long term administration of paroxetine at 6 months old.ResultsOur results showed that AD mice displayed emotional dysfunction in the early stage. Prophylactic administration of paroxetine ameliorated the initial emotional abnormalities and preserved the eventual memory function in AD mice.ConclusionOur data indicate that prophylactic administration of paroxetine ameliorates the emotional dysfunction and memory deficit in AD mice. These neuroprotective effects are attributable to functional restoration of glutamate receptor (GluN2A) in AD mice.

PSVI-34 Evaluating the impact of two Bacillus probiotic strains in commercial sows and their litters

Abstract The effect of long-term administration of two different Bacillus strains was tested on 90 breeding sows (Landrace x Yorkshire) that were randomly allotted into three treatments: a control group (CON), supplemented with 5x108 cfu/kg B. subtilis 25841 (PR1), or 5x108 cfu/kg B. amyloliquefaciens 25840 (PR2). Reproductive parameters were registered along three reproductive full cycles. Fecal samples were taken along the third cycle from the sows (on days 8 and 21 of lactation) and from the piglets (on days 21 and 33 (12 post-weaning)). Fecal microbiota was analyzed by sequencing the 16S RNA gene (Illumina MiSeq®) and jejunum samples, obtained from piglets on day 21, analyzed for gene expression (52 genes by OpenArray® plate). Supplemented sows showed higher number of born piglets per litter (P = 0.01) and PR2 sows a higher number of born alive (P = 0.01). Regarding sows’ fecal microbiota, changes were found in community structure (ANOSIM test, P = 0.08) with changes at phylum level (Firmicutes:Bacteroidetes: 3.7, 5.3 and 4.6 for CON, PR1 & PR2, P = 0.10) and at family level (Prevotellaceae: 9.4, 7.3, 7.3% (P = 0.03) and Ruminococcaceae: 16.1, 13.1, 13.7% (P = 0.04)). Several genera were also modified including Prevotella, Ruminococcus and Megasphaera. Regarding the microbiota of piglets, the administration of probiotics to their mothers was associated to structural changes in piglets’ fecal community during lactation (PEnvfit=0.05) but not after weaning, although relevant changes were observed between both periods (PEnvfit< 0.001). The expression of different genes was clearly modified by weaning but we were not able to detect changes related to the probiotic in any of the genes analyzed. In conclusion, the addition of B. subtilis 25841 and B. amyloliquefaciens 25840 were shown to enhance the sow reproductive performance in terms of prolificacy, with a clear impact on the gut microbial ecosystem of the sows and shifts in the microbiota structure of suckling piglets.

The effect of oral administration of green tea and ginger extracts on blood glucose in diabetic rats.

In recent years,green tea and ginger have become a subject of interest because of their beneficial effects on human health. The aim of the present study was to compare the effect of long term administration of green tea and ginger each alone to the effect of their combination on blood glucose level in streptozotocin-induced diabetic rats. Method: A group of 50 male albino rats was divided into five groups (10 rats each group). The normal control group( NC) administered tap water, other animals were injected by streptozotocin 45mg/Kg body weight intraperitonially to induce diabetes mellitus and then divided into four groups ,diabetic control (DC) without treatment, diabetic group administered green tea extract for four weeks (DGT), diabetic group administered ginger extract for four weeks(DGI), and diabetic group administered mixture of green tea and ginger for four weeks (DGG), then we compare the blood glucose level at 1st,2nd,3rd, and 4th week of experiment. Results:We observed that in groups whose water drink was substituted by green tea and ginger extract, the blood glucose level was significantly( p less than 0.05) reduced as compared to diabetic animals. Importantly, we observed that blood glucose level was near control level when green tea was administered simultaneously with ginger extract.Conclusion: Combination of green tea and ginger may be of great value as hypoglycemic agent in diabetic patients, the synergism of their effect on glucose regulation process is underlying this results.

Effect of Long Term-Administration of Aspartame on Sperm Quality, Testosterone and Oxidant Parameters in Mice

Effect of Long Term-Administration of Aspartame on Sperm Quality, Testosterone and Oxidant Parameters in Mice

Effect of long term Administration of hydrocortisone on some organs in females rats

Effect of long term Administration of hydrocortisone on some organs in females rats

The Effect of Long Term Administration of Aspartame on the Sciatic nerve of adult male albino rats and the Possible Therapeutic Role of Ozone (Histological and Biochemical Study)

Introduction: Aspartame is a widely used artificial non-nutritive sweetener, which replaced sucrose in foods for enhancing flavor while reducing calories. It was confirmed that aspartame was a multipotential carcinogenic agent increases the risk of lymphoma and neurological tumors.Aim of the work: This work is aimed to evaluate the effect of aspartame on the structure of the sciatic nerve and the possible role of ozone therapy.Material and methods: The present study was carried out on 30 adult male wister albino rats divided into three groups: control (I), aspartame(II) and ozone and aspartame treated (III) groups. Group (II) received aspartame (250 mg/kg/d) dissolved in distilled water and administered by gastric tube for 3 months. Group (III) received aspartame as in Group II, then received an ozone dose of 1.1 mg/kg/d intraperitoneal (IP) for 30 days. Rats were anesthetized and sciatic nerves were processed for light, electron microscope, morphometric and Real time-PCR analysis.Results: The sciatic nerve of aspartame group showed loss of regular architecture, separation of myelin lamellae with splitting of myeline sheath. Schwann cells appeared with vacuolated cytoplasm and collagen fibrils could be seen in the endoneurium. Immunohistochemically, there was decrease in expression of myeline basic protein (MBP) in myeline sheath and decrease in axon/fiber ratio (g ratio) statistically. Apparent structural and histomorphological improvement were noticed in ozone group.Conclusion: Aspartame induced histopathological changes in sciatic nerve. Our data suggests that ozone therapy has an important role in sciatic nerve regeneration by increasing the expression of neurotrophic and angiogenic factors establishing more favorable environment for nerve regeneration.

Long term treatment of metformin impedes development of chemoresistance by regulating cancer stem cell differentiation through taurine generation in ovarian cancer cells.

Development of resistance poses a significant challenge to effective first-line platinum based therapy for epithelial ovarian cancer patients. Cancer Stem Cells are envisaged as a critical underlying factor for therapy resistance. Thus, there is a critical need for developing approaches to diminish the enrichment of cancer stem cells and acquirement of resistance. Administration of metformin, a commonly prescribed drug against Type II diabetes exhibited promising effect in the management of ovarian cancer. However, the effect of long term administration of low dose of metformin as an adjuvant to cisplatin and paclitaxel during acquirement of chemoresistant phenotype has not been investigated so far. Using two isogenic cellular chemoresistant models (A2780 and OAW42) developed in the presence or absence of metformin, we demonstrated the ability of metformin to impede the development of resistance through increased drug sensitivity, increased proliferation, and reduced migratory abilities of the resistant cells. Metformin introduction also decreased the cancer stem cell population, expression of specific biomarkers and pluripotent genes. Further metabolic profiling of these cells using 1H-Nuclear Magnetic Resonance spectroscopy revealed significant modulation in taurine and histidine levels in resistant cells developed in the presence of metformin. Intriguingly, taurine treatment considerably reduced the cancer stem cell population and chemoresistance in resistant cells, indicating a novel role of taurine in differentiation of ovarian cancer stem cells. Altogether this is the first report on the potential role of metformin for targeting the cancer stem cell population via up regulation of taurine, leading to impediment in the acquirement of chemoresistance.

Protective Effect of Long Term Administration of Gum Arabic on Oxidative Stress in Hepatic Tissue of Diabetic Rats

Protective Effect of Long Term Administration of Gum Arabic on Oxidative Stress in Hepatic Tissue of Diabetic Rats

Curcumin (Curcuma longa Protects Against the Adverse Effect of Long Term Administration of Lithium on Cerebral and Cerebellar Cortices in Rats Histological and Immunohistochemical Study

Curcumin (Curcuma longa Protects Against the Adverse Effect of Long Term Administration of Lithium on Cerebral and Cerebellar Cortices in Rats Histological and Immunohistochemical Study

Black Cohosh (<i>Actaea racemosa</i> L.) Improves Serum Lipid Profiles and Vasomotor Responses in Ovariectomized Rats

We investigated the effects of long-term administration of black cohosh extract (BcEx) on serum lipid profiles and vasomotor responses in ovariectomized (OVX) rats and compared them with those of rats administered 17β-estradiol (E2) or raloxifene, a selective estrogen receptor modulator. Vehicle (OVX- or sham-control), BcEx (0.5 or 3.0 mg/kg/day), E2 (0.5 mg/kg/day), or raloxifene (2.5 mg/kg/day) were injected subcutaneously for 5 weeks, and serum lipid profiles and vasomotor responses were measured at the end of the treatment. BcEx lowered total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, but did not affect high-density lipoprotein cholesterol or triglyceride (TG) levels. Raloxifene showed a similar effect to that of BcEx, while E2 attenuated the increase in TC and LDL-C levels and significantly increased TG levels. The vascular relaxation induced by carbachol increased significantly in norepinephrine-precontracted aortic rings isolated from BcEx-, E2-, or raloxifene-treated rats. No change in uterine weight was observed in the BcEx-treated group. The raloxifene-treated group showed a similar trend as that of the BcEx-treated group, but E2 significantly increased uterine weight. These results suggest that long-term administration of BcEx behaves similar to the selective estrogen receptor modulator raloxifene.

Coronary angiogenic effect of long-term administration of Nigella sativa

BackgroundCoronary angiogenesis is one of the preferable adaptive responses of aerobic training. Previous studies found inotropic and hypertrophic cardiac effects for long-term administration of Nigella sativa (NS), but no studies have explored its coronary angiogenic effect. The present study compared the effect of long-term NS- administration and exercise training on the induction of coronary angiogenesis.MethodFifteen adult male Wistar rats were divided into three groups: control, NS-fed, and exercise-trained (Ex). The NS-fed rats were administered 800 mg/Kg NS orally for eight weeks. The (Ex) rats were trained on a five-lane treadmill at a speed of 18 m/min and a grade of 32° for two hour/day for eight weeks. After the experiment, the hearts were extracted and immunohistological slides were prepared using rat vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1), Von Willebrand factor (VWF) and nitric oxide synthase-2 (NOS-2) antibodies (Ab). Photomicrographs were analysed using ImageJ software, and the % of the immunostained-area of 10 fields per specimen was recorded.ResultVEGF was significantly higher in the NS- (2.59±1.37%) and Ex rats (2.51±1.86%) compared to the control group (1.58±0.78%) with P<0.01. The VWF was significantly lower in the two experimental groups (1.57±0.83%, 1.07±0.72%) for NS and Ex groups respectively, compared to the controls (2.38±1.72) with p<0.01. Only Ex group had a higher PECAM-1 (1.79±0.78%) and lower NOS-2 (0.83±0.57%) than the control group (1.19±1.17%, 1.25±1.19%) for PECAM-1 and NOS-2 with P<0.01 and P<0.05 respectively.ConclusionsThe present study demonstrated an increase in VEGF and a decrease of the VWF in the hearts of Nigella-fed and exercise-trained rats. This might indicate the potentiality for induction of coronary angiogenesis via long-term administration of NS and exercise training. NS effect on coronary angiogenesis needs to be explored further as it might lead to a new promising preventive and therapeutic agent of the ischemic heart disease.

Minocycline Protection against Paraquat Toxicity in &lt;I&gt;Drosophila melanogaster&lt;/I&gt;

We determined the effect of long-term administration (12 days) of minocycline (Mino) on the oxidative stress induced by paraquat (PQ) in D. melanogaster . After intoxication with PQ (40 mM) for 36 hours, the intoxicated group was subdivided in three groups: PQ (no further treatment after PQ intoxication), PQ-Mino (treated with Mino [0.05 mM] for 12 days after intoxication) and PQ-Control (exposed to PQ and maintained in standard medium for 12 days after intoxication). Two additional groups, not treated with PQ, were added: Control and Mino. After 36 hours intoxication the concentrations of H2O2, the activities of superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GSH-Px) and nitric oxide synthase (NOS) in the PQ group were increased, but the levels of nitrite and glutathione (GSH) were reduced with respect to the Control. In the group PQ also were observed an increase in the concentrations of MDA, protein carbonyl and the 8-hydroxydeoxyguanosine (8-OHdG) compared with Control. The post-treatment by 12 days with minocycline (PQ-Mino) mitigated oxidative damage induced by PQ as evidenced by the reduction in the concentration of the oxidative stress markers and by decrease damage to the lipid membrane (MDA), protein (protein carbonyl), DNA (8-OHdG) and in an increase of the extension of the life cycle of the flies with respect to PQ-Control.

Short- and Long-Term Effects of Methylphenidate on Cost-Benefit Decision Making in Adult Rats

Decision making is one of the most complicated and controversial topics in neuroscience. Today, there are important classes of chemicals that increase cognitive performance; in particular these are psychostimulants (e.g., methylphenidate, MPH). However, the long-term effects of MPH on cost-benefit decision making in healthy animals remain unknown. Therefore, we aimed to compare the short- and long-term effects of MPH in adult healthy male rats on the decision making in two distinct T-maze tasks and the ability of the animals to adjust the height of the obstacle in a T-maze or to process information on the reward amount. We found that short-term effects of MPH (2 weeks) played a significant role in making the correct decision in T-maze tasks, while the respective effects of long-term administration (12 weeks) were much weaker. These data suggest that chronic application of MPH has short- but not long-term effects on cost-benefit decision making in healthy adult animals.