José Javier Miguel-Hidalgo
Changes induced in the morphology and the multiplicity of functional roles played by astrocytes in brain regions critical to the establishment and maintenance of alcohol abuse suggest that they make an important contribution to the vulnerability to alcohol use disorders. The understanding of the relevant mechanisms accounting for that contribution is complicated by the fact that alcohol itself acts directly on astrocytes altering their metabolism, gene expression, and plasticity, so that the ultimate result is a complex interaction of various cellular pathways, including intracellular calcium regulation, neuroimmune responses, and regulation of neurotransmitter and gliotransmitter release and uptake...
2021: Advances in Neurobiology
Alexei Verkhratsky, Vladimir Parpura, Caterina Scuderi, Baoman Li
Major depressive disorder (MDD) presents multiple clinical phenotypes and has complex underlying pathological mechanisms. Existing theories cannot completely explain the pathophysiological mechanism(s) of MDD, while the pharmacology of current antidepressants is far from being fully understood. Astrocytes, the homeostatic and defensive cells of the central nervous system, contribute to shaping behaviors, and regulating mood and emotions. A detailed introduction on the role of astrocytes in depressive disorders is thus required, to which this chapter is dedicated...
2021: Advances in Neurobiology
John W Bigbee
The central nervous system is the last major organ system in the vertebrate body to yield its cellular structure, due to the complexity of its cells and their interactions. The fundamental unit of the nervous system is the neuron, which forms complex circuits that receive and integrate information and generate adaptive responses. Each neuron is composed of an input domain consisting of multiple dendrites along with the cell body, which is also responsible for the majority of macromolecule synthesis for the cell...
2023: Advances in Neurobiology
Jidong Fang, Patti Miller, Patricia S Grigson
INTRODUCTION: Sleep disturbances are prominent in drug use disorders, including those involving opioids in both humans and animals. Recent studies have shown that administration of liraglutide, a glucagon-like peptide-1 agonist, significantly reduces heroin taking and seeking in rats. In an effort to further understand the action of this substance on physiological functions and to evaluate safety issues for its potential clinical use, the aim of the present study was to determine whether the dose of liraglutide found effective in reducing responding for an opioid also could improve sleep in drug-naïve rats...
November 21, 2022: Brain Research Bulletin
Flaminia Coluzzi, Maria Sole Scerpa, Monica Rocco, Diego Fornasari
Opioids are widely used in cancer and non-cancer pain management. However, many transporters at the blood-brain barrier (BBB), such as P-glycoprotein (P-gp, ABCB1/MDR1), may impair their delivery to the brain, thus leading to opioid tolerance. Nonetheless, opioids may regulate P-gp expression, thus altering the transport of other compounds, namely chemotherapeutic agents, resulting in pharmacoresistance. Other kinds of painkillers (e.g., acetaminophen, dexamethasone) and adjuvant drugs used for neuropathic pain may act as P-gp substrates and modulate its expression, thus making pain management challenging...
November 16, 2022: International Journal of Molecular Sciences
Michael J Li, Steven J Shoptaw
It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non-randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal...
November 19, 2022: Addiction
Göran Hajak, Jan Hedner, Mirjam Eglin, Henrik Loft, Signe I Stórustovu, Simone Lütolf, Jonas Lundahl
OBJECTIVES: To evaluate the efficacy and safety profile of gaboxadol, a selective extrasynaptic GABA(A) agonist (SEGA) previously in development for the treatment of insomnia. METHODS: This was a randomised, double-blind, placebo-controlled, parallel-group, 2-week, Phase III study of gaboxadol 5, 10 and 15mg in outpatients meeting the DSM-IV criteria of primary insomnia (N=742). Zolpidem 10mg was used as active reference. RESULTS: At weeks 1 and 2, significant improvement in total sleep time (sTST) compared to placebo was seen for all doses of gaboxadol (all p<0...
August 2009: Sleep Medicine
Pavel A Markin, Natalia E Moskaleva, Svetlana A Lebedeva, Sergey V Kozin, Ekaterina M Grigorevskikh, Larisa G Kolik, Tatyana A Gudasheva, Svetlana A Appolonova
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family with diverse psychopharmacological effects including antidepressant and anxiolytic actions. However, the clinical use of BDNF is limited due to its poor pharmacokinetic properties. The development of low-molecular-weight BDNF mimetics passing through the blood-brain barrier is an emerging strategy for improved managing psychiatric diseases. The present study characterizes a novel dipeptide mimetic of the 2nd BDNF loop named GTS-201, which exhibits psychotropic properties in experimental animal models of anxiety and alcohol dependence...
October 28, 2022: Journal of Pharmaceutical and Biomedical Analysis
Angeliki M Angelidi, Matthew J Belanger, Alexander Kokkinos, Chrysi C Koliaki, Christos S Mantzoros
Recent insights into the pathophysiologic underlying mechanisms of obesity have led to the discovery of several promising drug targets and novel therapeutic strategies to address the global obesity epidemic and its comorbidities. Current pharmacologic options for obesity management are largely limited in number and of modest efficacy/safety profile. Therefore, the need for safe and more efficacious new agents is urgent. Drugs that are currently under investigation modulate targets across a broad range of systems and tissues, including the central nervous system, gastrointestinal hormones, adipose tissue, kidney, liver, and skeletal muscle...
May 12, 2022: Endocrine Reviews
Catherine M Cahill, Wendy Walwyn, Anna M W Taylor, Amynah A A Pradhan, Christopher J Evans
Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanistic differences both between agonists (agonist bias), and between μ- and δ-opioid receptors. In a process we will refer to as pass-forward allostasis, cells modified directly by opioid drugs impute allostatic changes to downstream circuitry...
November 2016: Trends in Pharmacological Sciences
K N Roy Chengappa, Jaspreet S Brar, Jessica M Gannon, Patricia J Schlicht
OBJECTIVE: To determine if adjunctive treatment with a standardized extract of Withania somnifera (WSE), with known anti-inflammatory and immunomodulating properties, improves psychopathology and stress in patients with schizophrenia or schizoaffective disorder (DSM-IV-TR). METHODS: Patients experiencing an exacerbation of symptoms were assigned to WSE (1,000 mg/d) or placebo for 12 weeks, added to their antipsychotic medication, in a random-assignment, double-blind, placebo-controlled study conducted from April 2013 to July 2016...
July 10, 2018: Journal of Clinical Psychiatry
Youna Vandaele, Eric Augier, Caroline Vouillac-Mendoza, Serge H Ahmed
When facing a choice, most animals quit drugs in favour of a variety of nondrug alternatives. We recently found, rather unexpectedly, that choice of the nondrug alternative is in fact inflexible and habitual. One possible contributing factor to habitual choice is the intermittency and uncontrollability of choice trials in previous studies. Here, we asked whether and to what extent volitional control over the occurrence of choice trials could change animals' preference by preventing habitual choice. To do so, rats were trained to nosepoke in a hole to trigger the presentation of two operant levers: one associated with cocaine, the other with saccharin...
November 2022: Addiction Biology
Xiao Lin, Ximei Zhu, Weiran Zhou, Zhibo Zhang, Peng Li, Guangheng Dong, Shiqiu Meng, Jiahui Deng, Lin Lu
The functional connectivity within and between networks could provide a framework to characterize the neurobiological mechanism of nicotine addiction. This study examined the brain regions that were functionally connected in response to smoking cues and established the brain-behaviour relationships in smokers. Sixty-seven male smokers were enrolled and scanned while performing the cue-reactivity and Stroop task. A whole-brain analysis approach, connectome-based predictive modelling (CPM), was conducted on the data from the cue-reactivity task to identify the networks that could predict the smoking severity with the Shen atlas as templates...
November 2022: Addiction Biology
Farhana Sakloth, Omar B Sanchez Reyes, Anne Ruiz, Andrew Nicolais, Randal A Serafini, Kerri D Pryce, Feodora Bertherat, Angelica Torres Berrio, Ivone Gomes, Lakshmi A Devi, Daniel Wacker, Venetia Zachariou
Opioid analgesics exert their therapeutic and adverse effects by activating mu opioid receptors (MOPR), however functional responses to MOPR activation are modulated by distinct signal transduction complexes within the brain. The ventrolateral periaqueductal gray (vlPAG) plays a critical role in modulation of nociception and analgesia, but the exact intracellular pathways associated with opioid responses in this region are not fully understood. We previously showed that knockout of the signal transduction modulator RGSz1 (RGSZ1KO) enhanced analgesic responses to opioids, while it decreased the rewarding efficacy of morphine...
October 30, 2022: Molecular Pharmacology
Paolo Poli, Luana Peruzzi, Pierdomenico Maurizi, Antonella Mencucci, Antonella Scocca, Simona Carnevale, Ottavia Spiga, Annalisa Santucci
BACKGROUND: The increase in the medical use of cannabis has revealed a number of beneficial effects, a variety of adverse side effects and great inter-individual variability. Association studies connecting consumption, addiction and side effects related to recreational cannabis use have led to the identification of several polymorphic genes that may play a role in the pharmacodynamics and pharmacokinetics of cannabis. METHOD: In total, 600 patients treated with cannabis were genotyped for several candidate polymorphic genes (single-nucleotide polymorphism; SNP), encoding receptors CNR1 and TRPV1; for the ABCB1 transporter; for biotransformation, bioactivation and biosynthesis; and CYP3A4, COMT and UGT2B7 conjugation...
October 11, 2022: Genes
Jinmeng Liu, Yemiao Gao, Chunxi Liang, Xia Liu
Background and aims: Nonsuicidal self-injury (NSSI) is highly prevalent in adolescents and is associated with various mental health problems. Repetitive NSSI (R-NSSI), as an extreme manifestation of NSSI, is a growing concern and has been proposed as a behavioral addiction. However, little is known about the potential addictive mechanisms of NSSI. This study aimed to examine the mediating effect of emotion dysregulation and the moderating effect of impulsivity using the Interaction of Person-Affect-Cognition-Execution (I-PACE) model in adolescents who repeatedly engage in NSSI...
October 25, 2022: Journal of Behavioral Addictions
Kishan V Patel, Sidharth Sahni, Lanvin F Taylor
Buprenorphine is a partial mu opioid agonist that has been increasingly utilized to treat patients with chronic pain and opioid use disorder (OUD). The drug has proven to provide significant chronic pain relief at low doses ranging from 75 to 1800 mcg. The conventional buprenorphine transitional process delays its introduction until patients begin withdrawal. However, this process can pose a barrier to both patients and providers due to some patients' inability to tolerate traditional prerequisite withdrawal...
October 25, 2022: Journal of osteopathic medicine
Laurent F Martin, Kevin Cheng, Stephanie M Washington, Millie Denton, Vasudha Goel, Maithili Khandekar, Tally M Largent-Milnes, Amol Patwardhan, Mohab M Ibrahim
Light therapy improves multiple conditions such as seasonal affective disorders, circadian rhythm dysregulations, and neurodegenerative diseases. However, little is known about its potential benefits in pain management. While current pharmacologic methods are effective in many cases, the associated side effects can limit their use. Non-pharmacological methods would minimize drug dependence, facilitating a reduction of the opioid burden. Green light therapy has been shown to be effective in reducing chronic pain in humans and rodents...
October 22, 2022: Journal of Pain
Harry Jarrett, Helene McNulty, Catherine F Hughes, Kristina Pentieva, J J Strain, Adrian McCann, Liadhan McAnena, Conal Cunningham, Anne M Molloy, Albert Flynn, Sinead M Hopkins, Geraldine Horigan, Ciara O'Connor, Janette Walton, Breige A McNulty, Michael J Gibney, Yvonne Lamers, Mary Ward
BACKGROUND: The generation of the active form of vitamin B6, pyridoxal 5'-phosphate (PLP), in tissues is dependent upon riboflavin as flavin mononucleotide, but whether this interaction is important for maintaining B6 status is unclear. OBJECTIVES: To investigate vitamin B6 and riboflavin status, their metabolic interaction and relationship with methylenetetrahydrofolate reductase (MTHFR) genotype in adulthood. DESIGN: Data from 5612 adults aged 18-102y were drawn from the Irish National Adult Nutrition Survey (NANS; population-based sample) and the Trinity-Ulster-Department of Agriculture (TUDA) and Genovit cohorts (volunteer samples)...
October 20, 2022: American Journal of Clinical Nutrition
Tamara Beetham, David A Fiellin, Susan H Busch
OBJECTIVES: To learn how preferences and practices regarding telehealth have evolved during the COVID-19 pandemic for physicians who provide opioid use disorder (OUD) treatment. STUDY DESIGN: Publicly registered physicians who provide OUD treatment were surveyed on their current and retrospective use of telehealth and how their perception of telehealth effectiveness and policy preferences have changed during the COVID-19 pandemic as telehealth regulations were loosened throughout the country...
September 2022: American Journal of Managed Care
2022-10-27 12:59:31
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