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
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
Liyana Hazwani Mohd Adnan, Nor Hidayah Abu Bakar, Nordin Simbak, Nasir Mohamad, Rusli Ismail, Nor Zidah Ahmad, Nor Suliana Mustafa, Nurul Farah Aina Md Fauzi
Opioids, amphetamines, and other types of substances have been widely abused around the world. Opioid dependence and tolerance are two distinct phenomena that have been associated with substance abuse issues. The management of its adverse consequences is becoming more challenging. More and more people are treated in Methadone Maintenance Therapy (MMT) program yet the issues are still unresolved. Researchers are continuing to study the best formulation in treating opioid dependent people starting with modern and alternative drug therapies...
July 2020: Iranian Journal of Basic Medical Sciences
Debra A Goff, Karri A Bauer, Julie E Mangino
BACKGROUND: Minocycline is an "old-drug" with Food and Drug Administration approval for the treatment of infection due to Acinetobacter species. The purpose of this study is to describe an Antimicrobial Stewardship Program's evaluation of minocycline for the treatment of patients with multidrug resistant A. baumannii (MDR-AB) infections. METHODS: This study evaluated hospitalized adult patients (September 2010 through March 2013) who received minocycline intravenously (IV) for a MDR-AB infection...
December 1, 2014: Clinical Infectious Diseases
Flavia S R Lopes, Aline C Giardini, Morena B Sant'Anna, Louise F Kimura, Michelle C Bufalo, Hugo Vigerelli, Vanessa O Zambelli, Gisele Picolo
Pain is a worldwide public health problem and its treatment is still a challenge since clinically available drugs do not completely reverse chronic painful states or induce undesirable effects. Crotalphine is a 14 amino acids synthetic peptide that induces a potent and long-lasting analgesic effect on acute and chronic pain models, peripherally mediated by the endogenous release of dynorphin A and the desensitization of the transient receptor potential ankyrin 1 (TRPA1) receptor. However, the effects of crotalphine on the central nervous system (CNS) and the signaling pathway have not been investigated...
September 30, 2022: International Journal of Molecular Sciences
Minsoo Kim, Mahnoor Mahmood, Ed Reznik, Payam A Gammage
Mitochondrial DNA (mtDNA) mutations are among the most common genetic events in all tumors and directly impact metabolic homeostasis. Despite the central role mitochondria play in energy metabolism and cellular physiology, the role of mutations in the mitochondrial genomes of tumors has been contentious. Until recently, genomic and functional studies of mtDNA variants were impeded by a lack of adequate tumor mtDNA sequencing data and available methods for mitochondrial genome engineering. These barriers and a conceptual fog surrounding the functional impact of mtDNA mutations in tumors have begun to lift, revealing a path to understanding the role of this essential metabolic genome in cancer initiation and progression...
August 27, 2022: Trends in Cancer
Arthur W Lambert, Diwakar R Pattabiraman, Robert A Weinberg
Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and we highlight the general principles of metastasis that have begun to emerge...
February 9, 2017: Cell
Vanina Popova, Ella J Daly, Madhukar Trivedi, Kimberly Cooper, Rosanne Lane, Pilar Lim, Christine Mazzucco, David Hough, Michael E Thase, Richard C Shelton, Patricio Molero, Eduard Vieta, Malek Bajbouj, Husseini Manji, Wayne C Drevets, Jaskaran B Singh
OBJECTIVE: About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants. This study compared the efficacy and safety of switching patients with treatment-resistant depression from an ineffective antidepressant to flexibly dosed esketamine nasal spray plus a newly initiated antidepressant or to a newly initiated antidepressant (active comparator) plus placebo nasal spray. METHODS: This was a phase 3, double-blind, active-controlled, multicenter study conducted at 39 outpatient referral centers...
June 1, 2019: American Journal of Psychiatry
Mu-Hong Chen, Chih-Ming Cheng, Ralitza Gueorguieva, Wei-Chen Lin, Cheng-Ta Li, Chen-Jee Hong, Pei-Chi Tu, Ya-Mei Bai, Shih-Jen Tsai, John H Krystal, Tung-Ping Su
Increasing evidence supports a rapid antidepressant and antisuicidal effect of a single subanesthetic dose of ketamine infusion for treatment-resistant depression (TRD). Maintaining the initial clinical response after ketamine infusion in TRD is a crucial next-step challenge. D-cycloserine (DCS), a partial agonist of the glycine co-agonist of the N-methyl-D-aspartate (NMDA) glutamate receptor, is potentially effective as a depression augmentation treatment. However, whether DCS maintains the antidepressant and antisuicidal effects of ketamine infusion remains unknown...
November 2019: Neuropsychopharmacology
Maurizio Fava, Marlene P Freeman, Martina Flynn, Heidi Judge, Bettina B Hoeppner, Cristina Cusin, Dawn F Ionescu, Sanjay J Mathew, Lee C Chang, Dan V Iosifescu, James Murrough, Charles Debattista, Alan F Schatzberg, Madhukar H Trivedi, Manish K Jha, Gerard Sanacora, Samuel T Wilkinson, George I Papakostas
Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties of a broad range of subanesthetic doses of IV ketamine among outpatients with treatment-resistant depression (TRD)...
July 2020: Molecular Psychiatry
Jennifer B Dwyer, Angeli Landeros-Weisenberger, Jessica A Johnson, Amalia Londono Tobon, José M Flores, Madeeha Nasir, Kevin Couloures, Gerard Sanacora, Michael H Bloch
OBJECTIVE: Adolescent depression is prevalent and is associated with significant morbidity and mortality. Although intravenous ketamine has shown efficacy in adult treatment-resistant depression, its efficacy in pediatric populations is unknown. The authors conducted an active-placebo-controlled study of ketamine's safety and efficacy in adolescents. METHODS: In this proof-of-concept randomized, double-blind, single-dose crossover clinical trial, 17 adolescents (ages 13-17) with a diagnosis of major depressive disorder received a single intravenous infusion of either ketamine (0...
April 1, 2021: American Journal of Psychiatry
Jennifer L Phillips, Sandhaya Norris, Jeanne Talbot, Meagan Birmingham, Taylor Hatchard, Abigail Ortiz, Olabisi Owoeye, Lisa A Batten, Pierre Blier
OBJECTIVE: Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance infusions. METHODS: Forty-one participants with treatment-resistant depression completed a single-site randomized double-blind crossover comparison of single infusions of ketamine and midazolam (an active placebo control)...
May 1, 2019: American Journal of Psychiatry
2022-10-17 05:56:01
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