Showing papers in "Neuropharmacology in 2017"

TL;DR: In 2014, the first illicit pills containing fentanyl, fentanyl analogs, and other novel synthetic opioids such as U-47700 were detected as mentioned in this paper, and since then, fentanyl has caused deaths in every state and fentanyl and its analogs have completely infiltrated the North American heroin supply.

TL;DR: The structural and functional dynamics of the gut microbiota and the signalling pathways of the brain‐gut axis are outlined and how kynurenine pathway metabolism may be regulated by microbial control of neuroendocrine function and components of the immune system is outlined.

TL;DR: The following overview focuses on areas of kynurenine research which are either controversial, of major potential therapeutic interest, or just beginning to receive the degree of attention which will clarify their relevance to neurobiology and medicine.

TL;DR: This review considers the current evidence for involvement of the KP in several neurological diseases, in biomarkers of disease and also the parallels that exist in KP metabolism with what is known in other diseases such as HIV, Alzheimer's disease/dementia, infection, immune privilege and cardiovascular disease.

TL;DR: Repeated cycles of alcohol and stress cause a progressive, persistent induction of HMGB1, miRNA and TLR receptors in brain that appear to underlie the progressive and persistent loss of behavioral control, increased impulsivity and anxiety, as well as craving, coupled with increasing ventral striatal responses that promote reward seeking behavior and increase risk of developing alcohol use disorders.

TL;DR: Some of the reasons for failure are reviewed, delineating both scientific and technical realities, some unique to the CNS, that have contributed to this, to suggest some changes that may improve outcomes in future CNS‐targeted drug discovery and development efforts.

TL;DR: Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia, particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment.

TL;DR: The clinical evidence supporting the role of psychological and physiological stress in instrumental motivation for alcohol consumption during the development of mild to moderate alcohol use disorders (AUDs) and in the compulsive, habitual alcohol consumption seen in severe, chronic, relapsing AUDs is detailed.

TL;DR: The emerging role of DNA damage and repair in functional recovery following stroke is discussed and the contribution of DNA repair to regenerative elements after stroke is highlighted.

TL;DR: The role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain is reviewed, and Elevating or enhancing EC signalling is antinociceptive in preclinical models.

TL;DR: Clinical trials using psychedelics pre and post prohibition are summarised, the methodological challenges of performing good quality trials in this area are discussed, and a strategic approach to the legal and regulatory barriers to licensing psychedelics as a treatment in mainstream psychiatry is considered.

TL;DR: Experimental studies strongly support inhibition of kynurenine aminotransferase (KAT) II as a novel target and a valuable pharmacological strategy in the treatment of psychosis and for improving cognitive performance relevant for schizophrenia.

TL;DR: Focusing on paradigmatic brain areas, such as hippocampus, striatum, and neocortex, typical and novel signaling mechanisms are reviewed, and the functional implications in normal brain function and brain diseases are discussed.

TL;DR: Preliminary interpretation of expected behavioral and physiological effects in man is allowed based on this preclinical data and comparison to both anecdotal human experience and multiple epidemiological surveys, which indicates that kratom exposure alone has not been causally associated with human fatalities to date.

TL;DR: Enthusiasm remains high for methods of minimally invasive clot removal as well as pharmacologic strategies to improve recovery after ICH, both of which are currently being evaluated in clinical trials.

TL;DR: An overview of the current state and advances in the field of viral vector-mediated gene therapy for neurological disorders is provided, as well as preclinical and clinical progress made thus far for brain cancer and various neurodegenerative and neurometabolic disorders.

TL;DR: Assessment of plasma Trp availability in health and disease requires measurement of concentrations of both free and total [Trp] in the first instance, followed, if necessary, by those of albumin and the physiological displacers ofalbumin‐bound Trp, non‐esterified fatty acids.

TL;DR: There is much still to learn about the biological mechanisms underlying how cannabis increases risk of psychosis, but there are plausible biological explanations for the psychotogenic effects of cannabis.

TL;DR: It is summarized that spreading depolarization is the electrophysiological correlate of the cytotoxic edema in various gray matter structures of the brain and vasogenic edema is the other major type of cerebral edema with relevance to ischemic stroke.

TL;DR: This review aims to highlight existing knowledge regarding how eCB signaling controls DA neuron function through modifications in synaptic strength at midbrain and striatal sites, and to raise outstanding questions on this topic.

TL;DR: The present article reviews the literature describing the synaptic effects of chronic alcohol exposure and their relevance for synaptic transmission in the central nervous system and focuses on the major excitatory and inhibitory neurotransmitters in the brain, glutamate and GABA, respectively, and how their neuroadaptations after chronic alcohol Exposure contributes to alcohol reinforcement, dependence and withdrawal.

TL;DR: It is proposed that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions.

TL;DR: The current understanding of the influence of KP enzyme expression and activity in different cell types on the pathophysiological mechanisms of specific neuropsychiatric diseases is discussed and the potential use of KP enzymes inhibition as a therapeutic strategy for treating neurological diseases is briefly discussed.

TL;DR: A growing body of evidence suggests that inflammation is associated with a dysregulation of the kynurenine pathway in suicidal patients, resulting in an imbalance of neuroactive metabolites that may contribute to the development of suicidality via changes in glutamate neurotransmission and neuroinflammation.

TL;DR: Evidence for stress-related neural, physiological, and behavioral changes associated with chronic alcohol exposure and withdrawal experience is presented and several pro-stress and anti-stress neuropeptide systems are focused on in contributing to the stress, negative emotional, and motivational consequences of chronic alcohol Exposure.

TL;DR: There is a great need for viable treatment strategies for CNS diseases, and it is believed that the preclinical success of FUS‐mediated BBB opening should encourage a rapid movement towards clinical testing, and the safety profile of the technique is high.

TL;DR: The results indicate that metformin provides neuroprotection against MPTP neurotoxicity, which might be mediated by inhibition of α-synuclein phosphorylation and induction of neurotrophic factors.

TL;DR: This review highlights evidence to indicate that the KP is a potential therapeutic target in both neurodegenerative and stress‐related neuropsychiatric disorders, and examines the efficacy, or lack thereof, of pharmacological modulators of the KP in neurological disorders.

TL;DR: The roles of sex‐ and age‐of‐animal, as well as the acquisition of AUDs, ethanol‐seeking and relapse continue to be factors and behaviors needing further study, while a substantial number of neurotransmitter and neuromodulatory system targets have been assessed.

TL;DR: A select group of genome‐wide association studies of alcohol dependence are presented, as one example of a way to generate functional hypotheses, within the addiction cycle framework, which may provide novel directions for validating the functional significance ofcohol dependence candidate genes.