Abstract
Herein, we investigated the role of periaqueductal gray (PAG)-resident microglia in the development of morphine tolerance and its underlying mechanisms. We showed that clodronate and minocycline known as microglia inhibitors reversed morphine tolerance, providing proof that microglia activation has key role in the development of morphine tolerance. The microglia-mediated anti-opioid mechanism occurs via sequential BDNF release and NMDA expression. Experimental evidence is provided here as conditional bdnf knockout mice (bdnf-/-) failed to develop tolerance following Cre-recombinase adenovirus treatment. Increased BDNF expression followed microglia activation in acute minocycline treatment reversible manner. Following BDNF release, NR2A subunit of NMDA receptor was upregulated in anti-BDNF reversible manner showing the contribution of BDNF signaling in the control of NMDA receptor expression following chronic morphine treatment. Our data provide compelling evidence that microglia activation and BDNF release are key regulators in opioid tolerance mechanism via glutaminergic synapse plasticity.
Keywords: Microglia, brain-derived neurotrophic factor, NMDA receptor, morphine tolerance, anti-opioid mechanism.
Current Pharmaceutical Design
Title:Microglia Activation Precedes the Anti-Opioid BDNF and NMDA Receptor Mechanisms Underlying Morphine Analgesic Tolerance
Volume: 19 Issue: 42
Author(s): Yosuke Matsushita, Idowu O. Omotuyi, Takehiro Mukae and Hiroshi Ueda
Affiliation:
Keywords: Microglia, brain-derived neurotrophic factor, NMDA receptor, morphine tolerance, anti-opioid mechanism.
Abstract: Herein, we investigated the role of periaqueductal gray (PAG)-resident microglia in the development of morphine tolerance and its underlying mechanisms. We showed that clodronate and minocycline known as microglia inhibitors reversed morphine tolerance, providing proof that microglia activation has key role in the development of morphine tolerance. The microglia-mediated anti-opioid mechanism occurs via sequential BDNF release and NMDA expression. Experimental evidence is provided here as conditional bdnf knockout mice (bdnf-/-) failed to develop tolerance following Cre-recombinase adenovirus treatment. Increased BDNF expression followed microglia activation in acute minocycline treatment reversible manner. Following BDNF release, NR2A subunit of NMDA receptor was upregulated in anti-BDNF reversible manner showing the contribution of BDNF signaling in the control of NMDA receptor expression following chronic morphine treatment. Our data provide compelling evidence that microglia activation and BDNF release are key regulators in opioid tolerance mechanism via glutaminergic synapse plasticity.
Export Options
About this article
Cite this article as:
Matsushita Yosuke, Omotuyi O. Idowu, Mukae Takehiro and Ueda Hiroshi, Microglia Activation Precedes the Anti-Opioid BDNF and NMDA Receptor Mechanisms Underlying Morphine Analgesic Tolerance, Current Pharmaceutical Design 2013; 19 (42) . https://dx.doi.org/10.2174/138161281942140105161733
DOI https://dx.doi.org/10.2174/138161281942140105161733 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Subject Index To Volume 12
Current Pharmaceutical Design Recent Updates in Imperative Natural Compounds for Healthy Brain and Nerve Function: A Systematic Review of Implications for Multiple Sclerosis
Current Drug Targets Medication-Induced Acute Abdominal Pain: Evaluation with CT Imaging
Current Medical Imaging Promoting Adult Hippocampal Neurogenesis: A Novel Strategy for Antidepressant Drug Screening
Current Medicinal Chemistry Emerging Therapy for Diabetic Neuropathy: Cell Therapy Targeting Vessels and Nerves
Endocrine, Metabolic & Immune Disorders - Drug Targets Role of Environmental Contaminants in the Etiology of Alzheimer’s Disease: A Review
Current Alzheimer Research Potentials of ES Cell Therapy in Neurodegenerative Diseases
Current Pharmaceutical Design Biochemical, Biomedical and Metabolic Aspects of Imidazole-Containing Dipeptides with the Inherent Complexity to Neurodegenerative Diseases and Various States of Mental Well-Being: A Challenging Correction and Neurotherapeutic Pharmaceutical Biotechnology for Treating Cognitive Deficits, Depression and Intellectual Disabilities
Current Pharmaceutical Biotechnology The “Parkinsonian Heart”: From Novel Vistas to Advanced Therapeutic Approaches in Parkinsons Disease
Current Medicinal Chemistry Adenosine Receptor Ligands in Clinical Trials
Current Topics in Medicinal Chemistry Anti-inflammatory strategies in stroke: a potential therapeutic target
Current Vascular Pharmacology The Vicious Circle of Leptin and Obesity
Current Nutrition & Food Science Anti-VEGF Therapy for Retinal Vein Occlusions
Current Drug Targets Targeting Class IIa HDACs: Insights from Phenotypes and Inhibitors
Current Medicinal Chemistry Comparative Anatomy, Physiology and In Vitro Models of the Blood-Brain and Blood-Retina Barrier
Current Medicinal Chemistry - Central Nervous System Agents Pharmacological Innovations for Posttraumatic Stress Disorder and Medication- Enhanced Psychotherapy
Current Pharmaceutical Design Potential Role of Calcium/Calmodulin-dependent Protein Kinase II to Angiogenesis Mediated Pathological Changes Seen in Osteoarthritis
Current Angiogenesis (Discontinued) Subject Index to Volume 2
Current Vascular Pharmacology Therapeutic Potential of Janus Kinase 3 (JAK3) Inhibitors
Current Pharmaceutical Design Tumor Bone Diseases: Molecular Mechanisms and Opportunities for Novel Treatments
Current Medicinal Chemistry - Anti-Cancer Agents