Cellular and Molecular Mechanisms of Addiction

2017 ◽  
Author(s):  
Kathryn J. Reissner ◽  
Peter W. Kalivas
Keyword(s):  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Drug Seeking ◽  
Molecular Changes ◽  
Cellular Changes ◽  
Continued Use ◽  
Brain Reward ◽  
Social Use ◽  
The Brain

Exposure to drugs of abuse can be a reinforcing experience that, in vulnerable individuals, can lead to continued use and the development of an addiction disorder. Evidence indicates that the escalation in use and compulsive motivation to obtain the drug is linked to long-lasting cellular changes within the brain reward neurocircuitry. In this chapter we describe the stages of transition in use from social use to habitual relapse, and within that context we describe the implicated neurocircuitry, and the enduring cellular and molecular changes that occur within that circuitry, that may mediate the preoccupation with drug seeking in addiction-vulnerable individuals.

Cellular and Molecular Mechanisms of Addiction

2013 ◽  
pp. 683-695
Author(s):  
Kathryn J. Reissner ◽  
Peter W. Kalivas
Keyword(s):  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Drug Seeking ◽  
Molecular Changes ◽  
Cellular Changes ◽  
Continued Use ◽  
Brain Reward ◽  
Social Use ◽  
Vulnerable Individual ◽  
The Brain

Exposure to drugs of abuse is for most individuals a reinforcing experience which can lead to continued use and the development of an addiction disorder. Evidence indicates that the escalation in use and ultimately compulsive motivation to obtain drug is linked to long lasting cellular changes within the brain reward neurocircuitry. In this chapter we will describe the transition in use from isolated social use to habitual relapse, and within that context will describe the neurocircuitry implicated in this process and the enduring cellular and molecular changes which occur within that circuitry that may mediate preoccupation with drug seeking in the addiction vulnerable individual.

scholarly journals Transcriptional mechanisms of drug addiction

2019 ◽  
Vol 21 (4) ◽  
pp. 379-387 ◽  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Noncoding Rnas ◽  
Brain Regions ◽  
Chromatin Modifications ◽  
Addictive Drugs ◽  
Functional Remodeling ◽  
Brain Reward ◽  
The Brain

Drugs of abuse can modify gene expression in brain reward and motivation centers, which contribute to the structural and functional remodeling of these circuits that impacts the emergence of a state of addiction. Our understanding of how addictive drugs induce transcriptomic plasticity in addiction-relevant brain regions, particularly in the striatum, has increased dramatically in recent years. 􀀬ntracellular signaling machineries, transcription factors, chromatin modifications, and regulatory noncoding RNAs have all been implicated in the mechanisms through which addictive drugs act in the brain. 􀀫ere, we briefly summarize some of the molecular mechanisms through which drugs of abuse can exert their transcriptional effects in the brain region, with an emphasis on the role for microRNAs in this process.

scholarly journals The effect of alcohol and nicotine abuse on gene expression in the brain

2009 ◽  
Vol 22 (2) ◽  
pp. 148-162 ◽  
Author(s):  
Traute Flatscher-Bader ◽  
Peter A. Wilce
Keyword(s):  
Gene Expression ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Human Subjects ◽  
Common Mental Disorder ◽  
Tobacco Consumption ◽  
Western World ◽  
Mesocorticolimbic System ◽  
The Brain

Alcohol intake at levels posing an acute heath risk is common amongst teenagers. Alcohol abuse is the second most common mental disorder worldwide. The incidence of smoking is decreasing in the Western world but increasing in developing countries and is the leading cause of preventable death worldwide. Considering the longstanding history of alcohol and tobacco consumption in human societies, it might be surprising that the molecular mechanisms underlying alcohol and smoking dependence are still incompletely understood. Effective treatments against the risk of relapse are lacking. Drugs of abuse exert their effect manipulating the dopaminergic mesocorticolimbic system. In this brain region, alcohol has many potential targets including membranes and several ion channels, while other drugs, for example nicotine, act via specific receptors or binding proteins. Repeated consumption of drugs of abuse mediates adaptive changes within this region, resulting in addiction. The high incidence of alcohol and nicotine co-abuse complicates analysis of the molecular basis of the disease. Gene expression profiling is a useful approach to explore novel drug targets in the brain. Several groups have utilised this technology to reveal drug-sensitive pathways in the mesocorticolimbic system of animal models and in human subjects. These studies are the focus of the present review.

scholarly journals Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk

2021 ◽  
Vol 22 (23) ◽  
pp. 13035
Author(s):  
Elisa Carloni ◽  
Adriana Ramos ◽  
Lindsay N. Hayes
Keyword(s):  
Brain Development ◽  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Disease Risk ◽  
Critical Role ◽  
Innate Immune ◽  
Immune Memory ◽  
Common Mechanism ◽  
The Impact ◽  
The Brain

Many types of stressors have an impact on brain development, function, and disease susceptibility including immune stressors, psychosocial stressors, and exposure to drugs of abuse. We propose that these diverse developmental stressors may utilize a common mechanism that underlies impaired cognitive function and neurodevelopmental disorders such as schizophrenia, autism, and mood disorders that can develop in later life as a result of developmental stressors. While these stressors are directed at critical developmental windows, their impacts are long-lasting. Immune activation is a shared pathophysiology across several different developmental stressors and may thus be a targetable treatment to mitigate the later behavioral deficits. In this review, we explore different types of prenatal and perinatal stressors and their contribution to disease risk and underlying molecular mechanisms. We highlight the impact of developmental stressors on microglia biology because of their early infiltration into the brain, their critical role in brain development and function, and their long-lived status in the brain throughout life. Furthermore, we introduce innate immune memory as a potential underlying mechanism for developmental stressors’ impact on disease. Finally, we highlight the molecular and epigenetic reprogramming that is known to underlie innate immune memory and explain how similar molecular mechanisms may be at work for cells to retain a long-term perturbation after exposure to developmental stressors.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

scholarly journals Learning of food preferences: mechanisms and implications for obesity & metabolic diseases

2021 ◽  
Author(s):  
Hans-Rudolf Berthoud ◽  
Christopher D. Morrison ◽  
Karen Ackroff ◽  
Anthony Sclafani
Keyword(s):  
Metabolic Diseases ◽  
Food Preferences ◽  
Reward System ◽  
Nutrient Sensing ◽  
Vagal Afferents ◽  
Dietary Knowledge ◽  
Ongoing Work ◽  
Brain Reward ◽  
The Brain ◽  
Vagal Function

AbstractOmnivores, including rodents and humans, compose their diets from a wide variety of potential foods. Beyond the guidance of a few basic orosensory biases such as attraction to sweet and avoidance of bitter, they have limited innate dietary knowledge and must learn to prefer foods based on their flavors and postoral effects. This review focuses on postoral nutrient sensing and signaling as an essential part of the reward system that shapes preferences for the associated flavors of foods. We discuss the extensive array of sensors in the gastrointestinal system and the vagal pathways conveying information about ingested nutrients to the brain. Earlier studies of vagal contributions were limited by nonselective methods that could not easily distinguish the contributions of subsets of vagal afferents. Recent advances in technique have generated substantial new details on sugar- and fat-responsive signaling pathways. We explain methods for conditioning flavor preferences and their use in evaluating gut–brain communication. The SGLT1 intestinal sugar sensor is important in sugar conditioning; the critical sensors for fat are less certain, though GPR40 and 120 fatty acid sensors have been implicated. Ongoing work points to particular vagal pathways to brain reward areas. An implication for obesity treatment is that bariatric surgery may alter vagal function.

scholarly journals Sublethal Exposure Effects of the Neonicotinoid Clothianidin Strongly Modify the Brain Transcriptome and Proteome in the Male Moth Agrotis ipsilon

Insects ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 152
Author(s):  
Camille Meslin ◽  
Françoise Bozzolan ◽  
Virginie Braman ◽  
Solenne Chardonnet ◽  
Cédric Pionneau ◽  
...  
Keyword(s):  
Sex Pheromone ◽  
Molecular Mechanisms ◽  
Insect Pest ◽  
Agrotis Ipsilon ◽  
Positive Effects ◽  
Male Moth ◽  
Hormetic Effect ◽  
Pest Insects ◽  
Neuronal Processes ◽  
The Brain

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids such as clothianidin. The residual accumulation of low concentrations of these insecticides can have positive effects on target pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction and olfactory synaptic transmission is cholinergic, neonicotinoid residues could indeed modify chemical communication. We recently showed that treatments with low doses of clothianidin could induce hormetic effects on behavioral and neuronal sex pheromone responses in the male moth, Agrotis ipsilon. In this study, we used high-throughput RNAseq and proteomic analyses from brains of A. ipsilon males that were intoxicated with a low dose of clothianidin to investigate the molecular mechanisms leading to the observed hormetic effect. Our results showed that clothianidin induced significant changes in transcript levels and protein quantity in the brain of treated moths: 1229 genes and 49 proteins were differentially expressed upon clothianidin exposure. In particular, our analyses highlighted a regulation in numerous enzymes as a possible detoxification response to the insecticide and also numerous changes in neuronal processes, which could act as a form of acclimatization to the insecticide-contaminated environment, both leading to enhanced neuronal and behavioral responses to sex pheromone.

scholarly journals DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The Past ◽  
Targeted Analysis ◽  
Lack Of Information ◽  
High Resolution Power ◽  
Resolution Level ◽  
Health And Disease ◽  
High Doses ◽  
The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

scholarly journals Molecular mechanisms of metabotropic GABAB receptor function

2021 ◽  
Vol 7 (22) ◽  
pp. eabg3362
Author(s):  
Hamidreza Shaye ◽  
Benjamin Stauch ◽  
Cornelius Gati ◽  
Vadim Cherezov
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Gabab Receptor ◽  
Neurological Diseases ◽  
Activation Mechanism ◽  
Allosteric Modulators ◽  
Inhibitory Neurotransmitter ◽  
Therapeutic Drugs ◽  
G Protein Coupled ◽  
The Brain

Metabotropic γ-aminobutyric acid G protein–coupled receptors (GABAB) represent one of the two main types of inhibitory neurotransmitter receptors in the brain. These receptors act both pre- and postsynaptically by modulating the transmission of neuronal signals and are involved in a range of neurological diseases, from alcohol addiction to epilepsy. A series of recent cryo-EM studies revealed critical details of the activation mechanism of GABAB. Structures are now available for the receptor bound to ligands with different modes of action, including antagonists, agonists, and positive allosteric modulators, and captured in different conformational states from the inactive apo to the fully active state bound to a G protein. These discoveries provide comprehensive insights into the activation of the GABAB receptor, which not only broaden our understanding of its structure, pharmacology, and physiological effects but also will ultimately facilitate the discovery of new therapeutic drugs and neuromodulators.

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