Background:Recent studies suggested that MPTP could cause gastrointestinal motility deficits additionally to its nonconclusive and controverted effects on the CNS (behavior and brain oxidative stress) in rats. A possible interaction between MPTP typical impairments and magnesium modulatory potential was previously suggested, as magnesium role was described in neuroprotection, gastrointestinal function, and oxidative stress.Aim:To investigate the possible modulatory effect of several magnesium intake formulations (via drinking water) in MPTP neurotoxicity and functional gastrointestinal impairment induction.Materials and Methods:Adult male Wistar rats were subjected to 3-week magnesium intake-controlled diets (magnesium depleted food and magnesium enriched drinking water) previously to acute subcutaneous MPTP treatment (30 mg/ kg body weight). Gastrointestinal motility (one hour stool collection test), and behavioral patterns (Y maze task, elevated plus maze test, open field test, forced swim test) were evaluated. Followingly, brain and bowel samples were collected, and oxidative stress was evaluated (glutathione peroxidase activity, malondial-dehyde concentrations).Results:MPTP could lead to magnesium intake-dependent constipation-like gastrointestinal motility impairments, anxiety- and depressive-like affective behavior changes, and mild pain tolerance defects. Also, we found similar brain and intestinal patterns in magnesium-dependent oxidative stress.Conclusion:While the MPTP effects in normal magnesium intake could be regarded as not fully relevant in rat models and limited to the current experimental conditions, the abnormalities observed in the affective behavior, gastrointestinal status, pain tolerance, peripheric and central oxidative status could be indicative of the extent of the systemic effects of MPTP that are not restricted to the CNS level, but also to gastro-intestinal system.

Background: As highlighted in ROME IV, irritable bowel syndrome (IBS) is a multifactorial psychosocial disorder marked by the presence of several changes in intestinal transit. Not only is difficult for patients to perform daily practice but for health professional as well since there is still uncertainty regarding the measurement of these symptoms and effect of prescribed treatment. Material and methods: This is why the present study aimed to assess the incidence of gastrointestinal symptoms through the VAS-IBS questionnaire in healthy Japanese individuals. To establish if there is causation, we also applied a dental anxiety form. Results: Following the allocation of both VAS-IBS and dental anxiety questionnaires, we observed that there are no statistically significant differences between sexes in terms of anxiety perceived regarding dental procedures (p >0.05). On the other hand, we noted that males are more prone to physical symptoms than women, especially abdominal pain and diarrhoea (p <0.05; Tukey HSD and Bonferroni for “abdominal pain” (p = 0.0229) and “diarrhoea” (p = 0.0181). Conclusions: In this way, the present study brings additional evidence regarding the usefulness of these questionnaires in human patients regardless of their health status.

Background: Pain, a distinctive undesirable experience, encompasses several different and fluctuating presentations across varying mood disorders. Therefore, the present narrative review aimed to shed further light on the matter, accounting for both experimental animal models and clinical observations about major depressive disorder (MDD) pathology. Method: Major databases were inquired from inception until April 2016 for records about MDD and pain. Results: Pain and MDD are tightly associated with each other in a bi-directional fashion. Several cross-sectional and retrospective studies indicated a high presence of pain in the context of mood disorders, including MDD (up to 65%), but also increased prevalence rates in the case of mood disorders documented among people with a primary diagnosis of either psychological or somatic pain (prevalence rates exceeding 45%). The clinical implications of these observations suggest the need to account for mood and pain manifestations as a whole rather than distinct entities in order to deliver more effective interventions. Limitations: Narrative review, lack of systematic control groups (e.g., people with the primary diagnosis at review, but not the associated comorbidity as a study) to allow reliable comparisons. Prevalence rates and clinical features associated with pain varied across different studies as corresponding operational definitions did. Conclusions: Pain may have a detrimental effect on the course of mood disorders-the opposite holds. Promoting a timely recognition and management of such an often neglected comorbidity would therefore represent a primary goal toward the delivery of effective, multi-disciplinary care.

Purpose Music therapy is widely used to enhance well-being, reduce pain, and distract patients from unpleasant symptoms in the clinical setting. However, the degree to which music modulates pain perception is unknown. The medial pain pathway including the limbic system is associated with emotion, but how music alters pathway activity is unclear. The aim of the study was to investigate pain thresholds and pain-related responses in the anterior cingulate cortex (ACC) and whether they were modulated when subjects listened to their favorite music genre. Subjects and Methods First, 30 subjects were examined for left forearm pain threshold using electrical stimulation with Pain Vision PS-2011N. The pain thresholds with and without music were compared. Second, when an 80-μA current from Pain Vision was applied to the left ankle of eight women, the pain-related responses of the ACC with and without music were observed with functional magnetic resonance device (fMRI). The changes in the pain-related activity in both parameters were discussed. Results The median pain threshold with favorite music was 38.9 μA, compared to 29.0 μA without, which was significantly different (p<0.0001). The men’s thresholds were significantly higher than women’s both with music (p<0.05) and without music (p<0.01). The pain threshold in women was more strongly affected by music than in men. The fMRI results showed that the pain-related response in the ACC in five of eight subjects was attenuated while they listened to their favorite music. No change was observed in the other three subjects. Conclusion The present findings suggest that pain perception might be strongly affected by listening to favorite music, possibly through modulation of pain-related responses in the ACC.

Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, Iasi, Romania Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 16th University Street, Iasi, Romania Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iași, Bd. Carol I, 20A, 700505 Iași, Romania Department of Oral Science, Matsumoto Dental University, Shiojiri, Japan

Lately there is an increased interest in understanding the biotechnological and possible treatment-related relevance of various natural extracts products in most of the current pathologies. Grape pomace extract was previously cited for its beneficial effects in some metabolic disorders, including diabetes. There is also a recent interest regarding the effects of grape pomace in the superior cognitive functions, however with some controversial results in this area of research. In the present paper we want to see the effects of 300 mg/kg grape pomace extract, 3 days per os administration, on the immediate spatial memory and possible locomotor activity (spontaneous alternations and number of arm entries, as tested in Y maze task), as well as on anxiety behaviour (time/number of arm entries in the open/closed arms of the maze, head drippings in the open arms, stretching in the closed arms and grooming behaviour) as tested in the elevated plus maze task in mice. In this report we present for the first time in our best of knowledge some anxiolityc effects of grape pomace, as demonstrated by the behavioral modifications in the elevated plus maze task (e.g. significant increase in the number of open arms entries), as well as some possible immediate (spatial) memory deficits as determined through the spontaneous alternations percentage in the Y maze task.

Background and objectives: The hormone oxytocin (OXT) has already been reported in both human and animal studies for its promising therapeutic potential in autism spectrum disorder (ASD), but the comparative effectiveness of various administration routes, whether central or peripheral has been insufficiently studied. In the present study, we examined the effects of intranasal (IN) vs. intraperitoneal (IP) oxytocin in a valproic-acid (VPA) autistic rat model, focusing on cognitive and mood behavioral disturbances, gastrointestinal transit and central oxidative stress status. Materials and Methods: VPA prenatally-exposed rats (500 mg/kg; age 90 days) in small groups of 5 (n = 20 total) were given OXT by IP injection (10 mg/kg) for 8 days consecutively or by an adapted IN pipetting protocol (12 IU/kg, 20 μL/day) for 4 consecutive days. Behavioral tests were performed during the last three days of OXT treatment, and OXT was administrated 20 minutes before each behavioral testing for each rat. Biochemical determination of oxidative stress markers in the temporal area included superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). A brief quantitative assessment of fecal discharge over a period of 24 hours was performed at the end of the OXT treatment to determine differences in intestinal transit. Results: OXT improved behavioral and oxidative stress status in both routes of administration, but IN treatment had significantly better outcome in improving short-term memory, alleviating depressive manifestations and mitigating lipid peroxidation in the temporal lobes. Significant correlations were also found between behavioral parameters and oxidative stress status in rats after OXT administration. The quantitative evaluation of the gastrointestinal (GI) transit indicated lower fecal pellet counts in the VPA group and homogenous average values for the control and both OXT treated groups. Conclusions: The data from the present study suggest OXT IN administration to be more efficient than IP injections in alleviating autistic cognitive and mood dysfunctions in a VPA-induced rat model. OXT effects on the cognitive and mood behavior of autistic rats may be associated with its effects on oxidative stress. Additionally, present results provide preliminary evidence that OXT may have a balancing effect on gastrointestinal motility.

Although the connections between neuropsychiatric and dental disorders attracted the attention of some research groups for more than 50 years now, there is a general opinion in the literature that it remains a clearly understudied and underrated topic, with many unknowns and a multitude of challenges for the specialists working in both these areas of research. In this way, considering the previous experience of our groups in these individual matters which are combined here, we are summarizing in this minireport the current status of knowledge on the connections between neuropsychiatric and dental manifestations, as well as some general ideas on how oxidative stress, pain, music therapy or even irritable bowel syndrome-related manifestations could be relevant in this current context and summarize some current approaches in this matter.

Lately there is an increased interest in understanding the possible relevance of oxytocin administration in the schizophrenic pathology. Also, currently in the literature there are models of schizophrenia, such as the one based on methionine administration, capable of replicating both positive and negative specific symptoms of schizophrenia, as well as the cognitive deficits from this disorder, which are believed to affect up to 75% of patients diagnosed with schizophrenia. In this context, in the present paper we were interested in preliminary revealing the effects of intraperitoneally oxytocin administration for 9 days, in a new approach, in a rat model of schizophrenia generated by administration of methionine for 2 weeks, on the memory and anxiety deficits induced by methionine administration (as studied in Y maze and elevated plus maze tasks), as well as on the oxidative stress markers (two antioxidant enzymes: superoxide dismutase-SOD and glutathione peroxidase-GPX, and the lipid peroxidation biomarker, malondialdehyde-MDA) from the temporal lobe. Our results showed some ameliorative effects of oxytocin administration on the immediate spatial memory (increased spontaneous alternation in Y maze) and anxiety-induced deficits (oxytocin increased the time spent in the open arms of the elevated plus maze) generated by the methionine-induced rat model of schizophrenia. Even more, oxytocin administration exerted some antioxidant effects in this model, as demonstrated by increased specific activity of GPX and reduced levels of MDA from the temporal lobe in the methionine + oxytocin group, as compared to the methionine group of rats. However, no significant modifications in SOD specific activity were found. This could have further relevance for the mechanistic behind the administration of oxytocin in the schizophrenia pathophysiology.

INTRODUCTION:Oxytocin (OT) is a well-known neuropeptides which together with vasopressin, melatonin, insulin and other hormones can alter both behavior and physiological or neuronal functions. This growing interest on OT roles is also based on the demonstrated beneficial effects as a stress reliever and a social bonding agent. The association between old age and OT was only vaguely studied. Little or few is known on the effect of the OT hormone on the old body. Hereby, we present our preliminary results in the research on behavioral changes regarding the intraperitoneal administration of OT in aged rats.SUBJECTS AND METHODS:OT was administered for 8 days in Wistar aged rats in parallel with saline administration for control group. Behavioral markers were assessed in some specific behavioral tasks, such as the Y-Maze test for short-term working memory, Open Field test, Elevated Plus Maze, and Forced Swim test for anxious and depressive behavior assessment, and Three-chambered Maze test for sociability assessment.RESULTS:Increased mobility and decreased anxiety behaviors were reported for the aged intraperitoneal OT-treated animals, as compared with controls, during FST and OFT, and respectively FST, EPM, and OFT. Also, decreased depressive-like behaviors were observed in the same animal group during FST and ST. Moreover, a decrease in anxiolytic behavior was observed as exposed to stressful stimuli (such as grooming behavior in OFT, and forced grooming behavior in ST), and as exposed to social stimuli (such as grooming behavior in TCT). Similarly, significant differences were obtained regarding the social behavior of the intraperitoneal OT-treated animal as compared to control group, the animals showing increased sociability and social preference for the stranger animal in TCT. However, no significant effects on the working memory (assessed as spontaneous alternation in YMT) were observed.CONCLUSIONS:Intraperitoneal administration of OT in aged rats has clear effects on anxious and depressive behavior, but no significant effects on the working memory. Also, several beneficial effects of OT on social preferences and sociability were observed.

Schizophrenia is an extremely complex psychiatric disease where perception of pain is altered, varying from abolition to lack of any kind of changes compared to normal controls and even hypersensitivity. In this way, the hypothesis of amending schizophrenia through pain therapy enhanced the importance of pain medication. But managing pain phenomenon in schizophrenia has large and unknown implications. Nevertheless, pharmacological interactions between the medications for these two entities are unknown and most likely would have a lot of side-effects and therefore ethnopharmacological methods became once again an interesting option. Traditional medicine wisdom was followed in the pursuit of finding connections between ancient knowledge and current scientific proven facts. To our best of knowledge, this is the first time when pain, plants and schizophrenia are discussed together. In this way, it seems that by replacing fully synthesized chemical products, the risk of side-effects decreases. Also, it appears that some plants besides treating pain may have curing effects on the psychotic activities in schizophrenia. Therefore, through this mini-review we emphasized on the advantages of the ethonopharmacological approaches in pain conditions in the context of schizophrenia, but also highlighted some cases of inappropriate usage of plants in traditional therapy.

Oxidative damage is a biochemical event currently incriminated in the occurrence of many disorders. The range of affections varies, from psychiatric illnesses, like depression, schizophrenia, Alzheimer's disease, for instance, to somatic disorders such as carcinogenesis or diabetes. Moreover, ophthalmological pathology is also affected in their development by the oxidative stress factor. In the present study, we focused on following the changes which occur in the serum of rats exposed to environmental stress conditions (swimming and treadmill exercises) by determinations of superoxide dismutase (SOD), glutathione peroxidase (GPX) specific activity and malondialdehyde (MDA) concentration. There are important biomarkers of oxidative stress, suspected to play a relevant role in the pathology of dry eye syndrome. Our preliminary oxidative stress analysis of the serum, sampled from animals exposed to physical stress in attempt to induce dry eye syndrome pathology, showed that the levels of SOD and GPX enzymes were higher as compared to controls. Also, MDA concentration was decreased with a significant value attributed to the swimmer rats compared to controls.

It is now generally accepted that animal studies are playing an important role in the understanding of anxiety disorders, since they contribute to the current knowledge regarding the mechanisms and possible therapeutic approaches in anxiety. In the present review we will detail some essential aspects of behavioral animal models of anxiety related to social defeat paradigm, elevated plus maze, elevated zero or T maze, light/dark box, social interaction test or tests based on predator models, considering the latest theories and methodological approaches in this area of research, as well as our previous studies focusing on anxiety manifestations in a variety of species including rats, zebrafish, dogs and pigs. Moreover, in this context, we will focus on the recent theories concerning oxidative stress, as well as importance of oxytocin administration (especially the intranasal route). This could be important considering that these two factors are currently being investigated as possible mechanisms (oxidative stress status) and related therapeutic target (both intranasal oxytocin and antioxidants) in the pathology of the anxiety disorders.

Pain phenomenon, the unpleasant sensory and emotional event, appears to evidently intrude in Parkinson disease (PD), a disease formally considered to be restricted only to motor deficits. Although over a half of persons with PD suffer from pain manifestations, there are very few reports targeting this issue. Considering the cases when motor symptoms of PD are eclipsed by severe pain disclosure, there is an obvious need of clarifying the intricate implications of pain in PD context. Because there are few studies researching the link between pain and PD in clinical context, but as well in animal models we chose to explore the effects of pain stimuli on a rodent model of PD. Materials and methods: We experimentally induced a PD model in Wistar rats (n=12) by injecting in the substantia nigra, a brain area known to be involved in PD occurrence, one dose of a 6-hydroxidopamine (6-OHDA) solution (8µm 6-OHDA base and 4µm physiological saline), utilizing neurosurgery, while their control peers received same dose of saline solution. Two weeks after the intervention the animals were subjected to the hot-plate test, a behavioral task for acquiring pain sensitivity. Results: There was noticed a statistical significant (F(1,10) = 5.67, p=0.038) sensibility of the 6-OHDA rats to thermal pain stimuli (8.2 s ± 0.8 s in 6-OHDA group) as compared to their peers (13.8 s ± 1.6 s in controls). Conclusions: The involvement of pain in PD animal models is demonstrated raising questions of how it influences PD evolution. Moreover, this result increases awareness of deficient diagnostic methods of pain in PD and as a consequence, poor treatment of pain manifestations.

Oxidative stress represents the imbalance between the production of reactive oxygen species and the organisms capacity to produce antioxidants. This phenomenon has captured lately a lot of attention, with an additional increased interest being manifested towards the relationship between psychological stress and oxidative stress. In the present study we decided to observe the changes which occur in stress environmental conditions applied to rats subjected to swimming and treadmill exercises, by focusing on a preliminary determination of (CAT) specific activity, an enzyme known to catalyse the decomposition of hydrogen peroxide into water and oxygen, and a valuable antioxidant protector, with possible implications into the dry eye pathology. Our results could suggest a possible dry eye animal model induced through stress and a possible implication of the oxidative stress markers in the occurrence of this ocular pathology, as suggested by the significant decrease in the CAT activity registered in rat tears collected after the application of environmental stressors (e.g. swimming and running) versus the control group.

Pain phenomenon, the unpleasant sensory and emotional event, appears to evidently intrude in Parkinson disease (PD), a disease formally considered to be restricted only to motor deficits. Although over a half of persons with PD suffer from pain manifestations, there are very few reports targeting this issue. Considering the cases when motor symptoms of PD are eclipsed by severe pain disclosure, there is an obvious need of clarifying the intricate implications of pain in PD context. Because there are few studies researching the link between pain and PD in clinical context, but as well in animal models we chose to explore the effects of pain stimuli on a rodent model of PD. Materials and methods: We experimentally induced a PD model in Wistar rats (n=12) by injecting in the substantia nigra, a brain area known to be involved in PD occurrence, one dose of a 6-hydroxidopamine (6-OHDA) solution (8μm 6-OHDA base and 4μm physiological saline), utilizing neurosurgery, while their control peers received same dose of saline solution. Two weeks after the intervention the animals were subjected to the hot-plate test, a behavioral task for acquiring pain sensitivity. Results: There was noticed a statistical significant (F(1,10) = 5.67, p=0.038) sensibility of the 6-OHDA rats to thermal pain stimuli (8.2 s ± 0.8 s in 6-OHDA group) as compared to their peers (13.8 s ± 1.6 s in controls). Conclusions: The involvement of pain in PD animal models is demonstrated raising questions of how it influences PD evolution. Moreover, this result increases awareness of deficient diagnostic methods of pain in PD and as a consequence, poor treatment of pain manifestations.

Sc varying from abolition to lack of any kind of changes compared to normal controls and even hypersensitivity. In this way, the hypothesis of amending schizophrenia enhanced the importance of pain medication. But managing pain phenomenon in schizophrenia has large and unknown implications. Nevertheless, pharmacological interactions between the medications for these two entities are unknown and mos side option. ancient knowledge and current scientific pr To our best of knowledge, this is the first time when pain, plants and schizophrenia are discussed together. In this way, it seems that by replacing fully synthesized chemical products, the risk of side have curing effects on the psychotic activities in schizophrenia. Therefore, through this mini ethonopharmacological approaches in pain conditions in the context of schizop highlighted some cases of inappropriate usage of plants in traditional therapy. Key activity in ethno

There is an increased interest in the current literature in how relevant the administration of oxytocin, mostly by using its intranasal administration, could be in some neuropsychiatric disorders and especially in those manifesting a deficit at their sociability level. These aspects made the possible usage of oxytocin as extremely attractive for some management and treatment solutions in the autistic pathology. Thus, we are describing here some original data and current literature status on how oxytocin could help pathophysiological autistic manifestations in both animal models and human patients, by mainly focusing on some specific behavioural or pain manifestations and related oxidative stress status.

In this report we will describe the effect of exercising (6 days, each day 3 separate training phases of 5 minutes each, on an adapted treadmill at 1.0 m/s) on oxidative stress status from the temporal lobe (expressed through 3 main parameters: superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA), as a marker of lipid peroxidation) and pain (as determined through 2 specific behavioural tasks such as hot plate test for the supraspinal acute thermal pain and the intra abdominal Zymosan administration for eliciting a local inflammatory reaction following responses to inflammatory visceral pain) in a rat valproic-acid induced perinatal model of autism, also trying to emphasize a possible implication of oxytocin in this complex pathological picture. We demonstrated here an increased oxidative stress status, as a result of treadmill exercising, in a VPA rat induced model of autism, as demonstrated mainly by a significant decrease in the specific activity of SOD (for the exercised VPA female rats), as well as a significant decrease of GPX specific activity in the male VPA exercised rats, when compared to non-exercised VPA groups, as well as the fact that the aforementioned series of exercises did not resulted in any changes of the pain perception of this rat models of autism, as studied in 2 pain-related behavioural tasks, independent to the gender of the rats with VPA model of autism.