4th Global Experts Meeting on Neuropharmacology September 14-16, 2016 San Antonio, USA

Dr. Valery Gmiro is the leading researcher of Institute Experimental Medicine (Russia). He has published more than 100 papers in reputed journals. The main scientific interest concerns the chemistry and pharmacology of biologically active compounds. He is the USSR State Prise Winner for the investigations in the field of physiology of synaptic transmission. During last years V.Gmiro is working on the problem of the creation of adaptogenic drugs acting through activation of afferent nerves. These drugs were shown to be effective tools to study the mechanisms of transmission of afferent signals and may be of interest in clinic using.

Porsolt test is a widely used animal model of depression in rats. Amitriptyline is a standard antidepressive drug used in high doses causing strong sedative side effect. Phenylephrine in high dose produced antidepressive effects without side sedative action. The aim of present work was to study the antidepressive and sedative effects of the combination amitriptyline in high and low doses with phenylephrine in threshold noneffective alone doses. Single i. m. injection of amitriptyline in rats in high doses of 10—30 mg/kg causes a weak antidepressive effect because only in 1.3—1.7 times decrease immobilization in Porsolt test. In the specified doses amitriptyline exhibits appreciable sedative effect because in 3—6 times decrease horizontal activity, and also in 2—2.5 times decrease vertical activity of rats in the open field test. Combined single i.m. injection of amitriptyline in a small dose of 3 mg/kg and high dose of 30 mg/kg with phenylephine in threshold, noneffective alone dose of 0.02 mg/kg, causes the maximal antidepressive effect because decreases immobilization in Porsolt test, accordingly, in 3 and 4.6 times, but does not produce side sedative effect in the open field test. The mechanism of potentiation of the antidepressive effect and elimination of the sedative side effect of amitriptyline is based on stimulation of gastric vagal mucosa afferents by phenylephine.

Sahar Mohamed Kamal Shams El Dine has received her MD in basic and clinical pharmacology from Pharmacology Department, Faculty of Medicine, Ain Shams University during the period of May 1997- May 2001. Currently, she is working as Professor of pharmacology in Ain Shams University. Her research has included CNS and CVS experimental work. She is serving as an Editorial Member of several reputed journals like Journal of Neurological Disorders & Expert Reviewers for journals like Journal of Experimental Pharmacology. She have authored 24 research articles. Her research articles are published on ResearchGate and www.academia.edu.

Quetiapine is a novel anti-psychotic drug. However, there is limited clinical evidence regarding prescribing patterns for quetiapine when used as maintenance treatment for bipolar disorder. Thirty-six albino rats were divided into 3 equal groups: control normal group [1] without exposure to chronic restraint for 6 hours daily/21 days, group [2] received DMSO 5% (v:v), as a solvent of quetiapine, with exposure to chronic restraint for 6 hours daily/21 days and group [3] received quetiapine 10 mg/kg/day i.p. for 3 weeks during exposure to chronic restraint for 6 hours daily/21 days. Intraperitoneal (i.p.) administration of quetiapine at a dose of 10 mg/kg/day for 3 weeks significantly (p<0.05) reduces the duration of immobility recorded by the Forced Swimming Test (FST) and significantly (p<0.05) increases the contents of GABA neurotransmitter in hippocampus homogenates. The present study adds a positive implication of quetiapine, as an antipsychotic drug, on both the immobility and the reduction of GABA content in hippocampus of albino rats exposed restraint model for 21 days.

Todd Lael Siler is an internationally recognized visual artist, author, and consultant. He received a PhD in Interdisciplinary Studies in Psychology and Art from the Massachusetts Institute of Technology in 1986, becoming the first visual artist to receive this doctoral degree at M.I.T. He began advocating the full integration of the arts and sciences in the 1970s. He founded The ArtScience Pro-gram, which pioneered arts-based learning methods and tools for cultivating innovation. The World Cultural Council awarded him the 2011 Leonardo DaVinci World Award of Arts, recognizing his lifelong practice of applying the “ArtScience” process to envision viable solutions to real-world global challenges.

All art and aesthetic experiences embody brain actions that encompass molecular and behavioral neuropharmacology. In fact, the whole process of making art, experiencing and appreciating art, as well as applying art in all-purpose ways to enrich our lives entails neurochemical interactions involving our central and peripheral nervous systems. We sense this first-hand the instant we’re attracted to or repelled by an artwork we like or dis-like; it’s evidenced by spikes in sensory evoked potentials or rapid rises in neurotransmit-ters norepinephrine and dopamine with sharp fluctuations in our heart rate and blood pressure. We know this when we self-discover how an artwork is relevant to our work and lives; a visceral connection is made that’s as visible as a surge of serotonin in the brain reward system. Our nervous systems are left feeling either inspired with wonder or agitated, dismayed or even depressed because we “didn’t get it”—as if there was some-thing more tangible to takeaway other than ephemeral experiences. This article addresses why and how art is much more than works of neurotransmitters, neuropeptides, neurohormones, enzymes, receptor proteins, ligand-gated ion channels (LGIC) receptors, neurotransmitter gamma-aminobutyric acid (GABA) receptors, and other brain mechanisms that enable and influence our creative acts of thinking, feeling, discovering, innovating, and communications. It is an amalgamation of these neural processes and products, which we freely interpret and use endlessly with imagination. Art remains a primary tool for researching and understanding the ever-evolving complexity and mysteries of human systems.

Leila Khalaj has completed her Pharm D. at the age of 24 and her PhD at the age of 30 from Shahid Beheshti University of Medical Sciences. She has done her postdoctoral studies in Neuroscience Research Center of Shahid Beheshti University and her sabbatical leave in Eskitis Institute for Cell and Molecular Therapies, Brisbane, Australia. She has published more than 14 papers in reputed journals, and currently she is an assistant professor in Alborz University of Medical Sciences, Alborz, Iran.

Two important pathophysiological mechanisms involved in cerebral ischemia are oxidative stress and inflammation. During pathological conditions such as brain ischemia, the ability of free radicals production is believed to be greater than their elimination by endogenous antioxidant systems, so brain is highly injured due to the oxidative and neuroinflammatory processes. Fibrates as peroxisome proliferator-activated receptor (PPAR)-α ligands, are reported to have antioxidant and anti-inflammatory actions. In this study, gemfibrozil, a fibrate is investigated for its therapeutic potential against global cerebral ischemia-reperfusion (I/R) injury of male and female rats. This study particularly has focused on inflammatory and antioxidant signaling pathways, such as nuclear factor erythroid-related factor (Nrf)-2, as well as the activity of some endogenous antioxidant agents. It was found that pretreatment of animals with gemfibrozil prior to I/R resulted in a sexually dimorphic outcome. Within females it proved to be protective, modulating inflammatory factors and inducing antioxidant defense system including superoxide dismutase (SOD), catalase, as well as glutathione level. However, Nrf-2 signaling pathway was not affected. It also decreased malondialdehyde level as an index of lipid peroxidation. In contrast, gemfibrozil pretreatment was toxic to males, enhancing the expression of inflammatory factors such as tumor necrosis factor-α, nuclear factor-κB, and cyclooxygenase-2, and decreasing Nrf-2 expression and SOD activity, leading to hippocampal neurodegeneration. Considering that gemfibrozil is a commonly used anti-hyperlipidemic agent in clinic, undoubtedly more investigations are crucial to exactly unravel its sex-dependent neuroprotective/neurodegenerative potential

Leila Khalaj has completed her Pharm D. at the age of 24 and her PhD at the age of 30 from Shahid Beheshti University of Medical Sciences. She has done her postdoctoral studies in Neuroscience Research Center of Shahid Beheshti University and her sabbatical leave in Eskitis Institute for Cell and Molecular Therapies, Brisbane, Australia. She has published more than 14 papers in reputed journals, and currently she is an assistant professor in Alborz University of Medical Sciences, Alborz, Iran.

Inducers of mitochondrial biogenesis are recently under investigation for use as a novel therapeutic approach in neurodegenerative disorders. Gemfibrozil, a fibrate, is clinically administered to control hyperlipidemia, and it secondarily prevents cardiovascular events such as cardiac arrest in susceptible patients. The ability of Gemfibrozil is investigated for the first time to modulate mitochondrial pro-survival factors involved in the mitochondrial biogenesis signaling pathway, including peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factor (NRF-1), and mitochondrial transcription factor A (TFAM) in the brain of both sexes of rats undergoing Ischemia-reperfusion (I/R). To induce I/R injury in rats, 4-vessels occlusion model was used. Gemfibrozil was administered to animals through gavage. Data collection was performed using western blotting, as well as histological and antioxidant enzyme assays. Pretreatment of animals with gemfibrozil prior to I/R resulted in a sexually dimorphic outcome. While the expression of NRF-1 and TFAM were induced in gemfibrozil-pretreated met-estrous females, they were suppressed in males. Gemfibrozil also proved to be neuroprotective in met-estrous females, as it inhibited caspase-dependent apoptosis while in males it led to hippocampal neurodegeneration via activation of both the caspase-dependent and caspase-independent apoptosis. In the mitogen-activated protein kinase (MAPKs) pathway, gemfibrozil pretreatment induced the expression of extracellular signal-regulated kinases (ERK1/2) in met-estrous females and reduced it in males. These findings correlatively point to the sexual-dimorphic effects of gemfibrozil in global cerebral I/R context, especially through modulation of the mitochondrial biogenesis pathway, as well as MAPKs and apoptotic cell death pathways.

Mr.Abdul Khayum K has received his Masters of Pharmacy in Pharmacology from PSG College of Pharmacy, Coimbatore during the period 2012-2014. Currently, he is working as Assistant Professor in Department of Phamacology, Faculty of Pharmacy, Karpagam University. His research interest includes Neuroischemia, Ischemic Stroke models and animal behavior studies.

The hypothesis of the present study is that N-methyl D-aspartate (NMDA) receptor antagonist and 5-hydroxy tryptamine (5- HT1a) agonist will restore brain serotonin levels and can have role in the treatment of depression. Depression hypothesis is majorly based on neurochemical alteration. The neurotransmitters like serotonin, nor epinephrine, dopamine and glutamate have a strong interlink. The mice were divided into 7 groups consisting of 6 animals each. Depresson was induced with P-chlorophenylalanine (PCPA). On first day 300 mg/kg and on alternative days 100 mg/kg was administered to all the groups. The drug treatment memantine, 8-OH DPAT and their combinaiton was continued for 14 days. Fluoxetine was used as a positive control. Behavioral screening, neurotransmitters and neurochemical were measured in different regions of control and serotonin depleted mice brain to assess the anit depressant property of the drugs. The histopathological examination was also carried out. The results have shown that, depletion of brain serotonin level with PCPA treatment and resulted in reduced locomotion, anxiety behavior and ambulation with no alteration in rearing and grooming behaviours. The NMDA antagonist memantine, 5-HT1a agonist 8-OH DPAT and their combination have shown no significant change in locomotion. Whereas memantine 40 mg/kg have shown increased anxiolytic activity. The mice treated with memantine and its combination with 8-OH DPAT have shown significant change in force swim test. In neurotransmitters, the memantine and 8-OH DPAT group exhibited significant reduction in glutamate and aspartate levels, whereas GABA levels were increased. Histopathological report shows focal areas of degeneration in cerebrum region with PCPA treatment and drug treamtents restored the morphology of the brain. Hence, it can be concluded that, memantine, 8-OH DPAT and thier combination have better result in improving the depressive symptoms induced with PCPA than the positive control fluoxetine.

Liudmyla D. Popova has PhD degree, degree of doctor of biology sciences, the title of Biochemistry Department Professor. She is presently Biochemistry Department professor in Kharkiv National Medical University, Ukraine. Oxana A. Nakonechnaya has PhD degree, degree of doctor of medicine, the title of Biochemistry Department Professor. She is presently Head of Biochemistry Department in Kharkiv National Medical University, Ukraine. Irina M. Vasylyeva has PhD degree. She is presently Biochemistry Department assistant in Kharkiv National Medical University.

High anxiety is the base not only for depression development but also to impulsive aggression manifestation. We revealed the differences in neurohumoral status in animals with submissive and dominant behavioral types. Hypothalamic pituitary adrenal axis hyperactivity, the increase in noradrenaline and the decrease in serotonin levels in limbicocortical regions were observed in submissive male rats (high anxiety). Due to these results, we studied interrelation between anxiety level and aggressiveness index. The study involved 100 young men aged 18 to 22 years. They were asked to answer Buss-Durkee Hostility Inventory and Spielberger State-Trait Anxiety Inventory. The anxiety level was assessed in points. The aggressiveness index was estimated in a percentage of the maximum level. No correlation between the anxiety level and the aggressiveness index was found in whole group. We divided whole group into three subgroups depending on anxiety level: with high, moderate and low anxiety levels. It should be noted, that the most of men had moderate anxiety level, a few men had low anxiety level. We revealed the existence of high positive correlation between anxiety level and aggression index in men with high anxiety level and negative correlation between these two parameters in men with low anxiety level. In last subgroup correlation was statistically insignificant due to a few men with low anxiety level. In men with moderate anxiety level no correlation between anxiety level and aggression index was observed. This interrelation may be taken into account in anxiety treatment and in the prevention of impulsive aggression manifestation .

Dr. Eleni Konsolaki is a psychologist with expertise in the biological basis of cognitive functions. After two master\'s degrees in cognitive science and statistics, she received her PhD in neuroscience from the Biomedical Research Foundation of the Academy of Athens (in collaboration with the University of Athens). Her work which has been supported by Onassis and Propondis Foundations and the Foundation for Education and European Culture has been published in peer-reviewed journals and awarded from the University of Athens. At present, she is instructor at Deree-The American College of Greece and external collaborator of the University and TEI of Athens.

Animal models are widely used in experimental pharmacological protocols in order to study drug effects on neural function underlying specific behaviors. This is the reason why the protocols include behavioral experiments to assess the performance of the animals in several cognitive or mobility tasks. These preclinical studies are important in the development of drugs for the treatment of neuropsychiatric disorders. However, translational failure continues to be a challenge for the neuropharmacological field as the results of these early phase studies fail to predict the results of phase III or randomised clinical trials. The present study proposes a novel approach for the successful transition from animal studies to the clinic: the measurement of ecological variables even in demanding behavioral tasks. One characteristic of the behavioral experiments is the simultaneous recording of various variables during only one behavioral task. Statistical significant differences between experimental and controls groups are then reported and terms such as “anxiety-like” or “depression-like” are used in order to interpret the behavioral performance based on the similarity with the human behavior/symptoms. We suggest that following the ethological perspective we tend to avoid vague categorization and we may overcome the potential impediments of translational failure. We compared C57Bl/6J mice behavioral task performance in the literature with and without ecological variables either measured in species-specific behavioral tasks or in cognitive tasks (as qualitative variables) and we found completely different behavioral phenotypes. Our study sheds light on the crucial role of ecological variables and how they may alternate behavioral data interpretation.

Patrizia Proia has completed his PhD in Neuroscienze at the age of 34 years from Palermo University and postdoctoral studies on perfoming enhancing of anabolic androgenic steroids from University of Maryland. She is an assistant professor in biochemestryand she has published more than 20 papers in reputed journals and has been serving as a reviewer of repute. She now start a new multidisciplinary approach in order to analyze the effect of the exercise in patological and healthy people investigating the neurobiology response (on neurotrophines, hormones and protein stress related), genetic background and psycological assessment.

The aim of this study is to investigate the neurobiology of stress/emotionality, creating a multidisciplinary assessment model, which can help to provide psychological and physiological responses depending on the genetic background related to sport performances, social closeness and performance anxiety management in team sports.rnWe enrolled 20 female volleyball players aged 13 ± 1 years old played in two different teams during a regional championship final. Saliva collection was carried out before and after the match. In order to evaluate the neuroendocrine effectors involved in stress and performance, we analyzed cortisol and progesterone levels through Elisa standard kit as well as HSP70 and amylase activity as stress-induced markers. As concern the psychometric assesment, we administrated he CSAI-2 test, Closeness Generating Procedure and STAI test. Genomic DNA was isolated from saliva cells using a QIAamp saliva kit according to the manufacturer’s protocols. The SNP of the 5-HTTLPR, BDNF, DRD4 were analyzed.rnThe results of the T-test performed on the total results showed a statistically significant relationship (p < 0.05) in cortisol levels pre and post match, as well between amylase and HP70 according to the genetic background. The analysis performed using just post match samples show a negative correlation between social closeness, cortisol and progesterone levels, with p < 0.010 for progesterone vs social closeness and p < 0.012 for cortisol vs social closeness. About the winner teams and the looser teams, there is a negative correlation between pre match cortisol levels and performance anxiety (p < 0.042).rn