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New frontiers in the neuropsychopharmacology of mental illness

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194049 Year: Pages: 254 DOI: 10.3389/978-2-88919-404-9 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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In recent years, mental illnesses have become recognized as a huge emotional and financial burden to the individual, their relatives and society at large. Stress-related and mood disorders as well as psychoactive substance abuse are among the disorders associated with most disability in high income countries. Suicide, which is often attributed to some underlying mental disorders, is a leading cause of death among teenagers and young adults. At the same time, mental disorders pose some of the toughest challenges in neuroscience research. There are many different categories of mental disorder as defined and classified by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the International Statistical Classification of Diseases 10th Revision (ICD-10). Despite the ongoing improvements of those widely used manuals, the validity and reliability of their diagnoses remain a constant debate. However, it has now become accepted by the scientific community that mental disorders can arise from multiple sources. In that regard, both clinical and animal studies looking at gene-environment interactions have helped to better understand the mechanisms involved in the pathophysiology as well as the discovery of treatments for mental disorders. This Research Topic aims to cover recent progress in research studying how genetic make-up and environmental factors (such as stress paradigm or pharmacological treatment) can contribute to the development of mental disorders such as anxiety, depression, and schizophrenia. This Research Topic also seeks to highlight studies looking at affective-like disorders following the intake of drugs of abuse. We also welcome all research articles, review papers, brief communications, and commentary on topics related to the broad field of Neuropsychopharmacology.

Opioids: Addiction, Narrative, Freedom

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ISBN: 9781947447837 9781947447844 Year: Pages: 190 DOI: 10.21983/P3.0210.1.00 Language: English
Publisher: punctum books
Subject: Social Sciences
Added to DOAB on : 2019-03-26 11:21:04
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An epidemic is a feeling set within time as much as it is a matter of statistics and epidemiology: it is the feeling of many of us in the same desperate place at the same desperate time. Opioid epidemic thus names a present moment — at once historic and historical — centered on the substance of opioids as much as it names the urgency of all of us who are currently in proximity to these substances. What is the relationship between these historic and historical moments, the present moment, the history of pharmacological capitalism, and a set of repeated neurological activities, as well as human loss and desire, that has fueled the exponential rise in the rates of opioid use and abuse between 2000-2018? Opioids: Addiction, Narrative, Freedom is an auto-ethnography written from deep within—biologically within—this opioid epidemic. Tracing opioids around and through the bodies, governmental, and medical structures they are moving and being moved through, Opioids is an examination of what it means to live within an environment saturated with a substance of deep economic, political, neuroscientific, and pharmacological implications. From exploring media coverage of the epidemic and emerging medical narratives of addiction to detailing the legal inscription of differences between “pain patients” and people addicted to drugs, Opioids consistently asks: what is it like to live within an epidemic? What forms of freedom become possible when continually modulated by our physical experiences of the material proximities of an epidemic? How do you live with something for a long time

Neuroactive metabolites of ethanol: a behavioral and neurochemical synopsis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193752 Year: Pages: 126 DOI: 10.3389/978-2-88919-375-2 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-19 16:29:12
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Ethanol is a very elusive drug, which has mechanisms of action that are diverse and relatively non-selective. Moreover, ethanol has been demonstrated to be a biologically active substance by itself, but also a pro-drug of the neuroactive metabolites, acetaldehyde and acetate. Acetaldehyde has traditionally been known as a toxic substance with several effects on multiple systems. However, in the last few decades evidence has accumulated to reveal the specific and, in some instances, distinct neural actions of acetaldehyde and acetate that are in part responsible for some of the observed psychoactive effects of ethanol. The present issue will address these challenges to provide an up-to-date synopsis of the behavioral and neurophysiological impact of the two direct metabolites of ethanol, acetaldehyde and acetate. In doing so, this issue will present human and rodent evidence on their behavioral and neurophysiological impact, either when administered alone as drugs, or when metabolically-derived from their parent compound. Emphasis will be placed to stress the importance of the different enzymatic systems that intervene to produce these metabolites, either peripherally and/or directly in the brain. Similarly, this Research Topic will be aimed at addressing some of the possible mechanisms of action of acetaldehyde and acetate in different brain areas and in different intracellular systems. Furthermore, the issue will lay out some of the suggested mechanisms of action of ethanol and of its metabolites by which they form adducts with other molecules and neurotransmitters such as dopamine and opioids (which lead to salsolinol and tetrahydropapaveroline, respectively), and their impact on the synthesis and actions of neuromodulators such as adenosine and the cannabinoid system.

Keywords

Ethanol --- Catalase --- acetate --- Dopamine --- Salsolinol --- Opioids --- Addiction --- Drug abuse

Food cravings

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195176 Year: Pages: 101 DOI: 10.3389/978-2-88919-517-6 Language: English
Publisher: Frontiers Media SA
Subject: Psychology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Food craving refers to an intense desire or urge to consume a specific food. In Western or Westernized societies, these craved foods usually have high palatability and are energy dense, that is, they have high sugar and/or fat content. Accordingly, the most often craved food is chocolate. Food craving is a multidimensional experience as it includes cognitive (e.g. thinking about food), emotional (e.g. desire to eat or changes in mood), behavioral (e.g. seeking and consuming food), and physiological (e.g. salivation) aspects. Experiences of food craving are common, that is, they do not reflect abnormal eating behavior per se. However, very intense and frequent food craving experiences are associated with obesity and eating disorders such as bulimia nervosa and binge eating disorder. The aim of this research topic was to gather new contributions to a variety of aspects of food craving, which include its assessment, cognitive and emotional triggers, moderators, and correlates of food craving, and the relevance of food cravings in clinical issues, among others.

Attachment Assessment in treatments, prevention and intervention programs

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195237 Year: Pages: 104 DOI: 10.3389/978-2-88919-523-7 Language: English
Publisher: Frontiers Media SA
Subject: Psychology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Attachment theory, assessment and research offers a broad, far-reaching view of human functioning, and it can enrich a psychologist's understanding of subjects and their relational adjustment, both in clinical and non-clinical settings. Ongoing research in attachment has led to a number of individual treatments and prevention and intervention programs. The assessment of an individual's attachment organization, can play a crucial role in explaining and previewing the unfolding treatment, the relational adjustments or concerns, and the psychological well-being. We hope to receive empirical papers that give evidence for the usefulness of attachment assessment in both clinical (e.g., patients with Eating Disorder; or Axis-II; psychotherapy patients…) or not clinical population (e.g. Adoptive and/or foster families or couples, Mother-infant assessment in prevention field…). These papers should include methodological issues and information about the participants, the methods used to assess attachment, the process of scorer training and the availability of the manual used to obtain inter-scorer reliability. Case studies may be of interest to the extent that they demonstrate the value of a systematic approach to attachment material. A range of theoretical perspectives is welcome as well presentation of new emergent tools on attachment. Because Frontiers in Psychology is an international journal, each empirical paper should comment on the international implications of the findings and discuss its cross-cultural use. Such comments may include, for example, its linguistic specificity, its robustness in translation, and the cross-cultural generalizability of the constructs and behaviors of the measure and its usual correlates. Cross-cultural generalizability is not, however, a requirement.

Keywords

Attachment --- Parenting --- Trauma --- Anorexia --- Addiction --- Obesity --- autism --- Adoption --- Treatment

Neural circuits underlying emotion and motivation: Insights from optogenetics and pharmacogenetics

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195343 Year: Pages: 172 DOI: 10.3389/978-2-88919-534-3 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2015-12-10 11:59:06
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Application of optogenetic and pharmacogenetic tools to study the neural circuits underlying emotional valence, feeding, arousal and motivated behaviors has provided crucial insights into brain function. Expression of light sensitive proteins into specific neurons and subsequent stimulation by light (optogenetics) to control neuronal activity or expression of designer receptors exclusively activated by designer drugs (DREADD) in specific neuronal populations with subsequent activation or suppression of neuronal activity by an otherwise inert ligand (pharmacogenetics) provides control over defined elements of neural circuits. These novel tools have provided a more in depth understanding into several questions about brain function. These include: • Regulation of sleep-wake transition by the interaction of hypocretin neurons of lateral hypothalamus and nor adrenergic neurons of the locus coruleaus • Regulation of feeding by AGRP and POMC neurons in arcuate nucleus of the hypothalamus • Place preference and positive reinforcement by activation of DA neuron of VTA • Place aversion by activation of VTA GABA and lateral habenula neurons • Opposing influences on reinforcement by activation of D1 and D2 expressing medium spiny neurons of dorsal striatum and nucleus accumbens The list still grows... From cell type specific manipulations to signaling properties in the cell (Dietz et al 2012) with unprecedented temporal resolution, these tools revolutionize the exploration of pathways/connectivity. Recent years also witnessed the extension of applying these tools from studying emotional valence and motivated behavior to reactivation of memory. c-fos based genetic approaches allowed us to integrate light sensitive opsins or DREADD receptor into specific neurons that are activated by certain learning events (for example fear) (Garner et al 2012; Liu et al 2012). In this Research Topic, we welcome researchers to contribute original research articles, review articles, methods and commentary on topics utilizing optogenetic and pharmacogenetic tools to study the neural circuits underlying emotional valence, motivation, reinforcement and memory. We believe the Research Topic will shine light on various questions we have about brain function by using novel optogenetic and pharmacogenetic tools and will hopefully inspire ongoing research to overcome the hurdles of using these tools to advance clinical applications.

Neuronal and Psychological Underpinnings of Pathological Gambling

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193202 Year: Pages: 132 DOI: 10.3389/978-2-88919-320-2 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Like in the case of drugs, gambling hijacks reward circuits in a brain which is not prepared to receive such intense stimulation. Dopamine is normally released in response to reward and uncertainty in order to allow animals to stay alive in their environment – where rewards are relatively unpredictable. In this case, behavior is regulated by environmental feedbacks, leading animals to persevere or to give up. In contrast, drugs provide a direct, intense pharmacological stimulation of the dopamine system that operates independently of environmental feedbacks, and hence causes “motivational runaways”. With respect to gambling, the confined environment experienced by gamblers favors the emergence of excitatory conditioned cues, so that positive feedbacks take over negative feedbacks. Although drugs and gambling may act differently, their abnormal activation of reward circuitry generates an underestimation of negative consequences and promotes the development of addictive/compulsive behavior. In Parkinson’s and Huntington’s disease, dopamine-related therapies may disrupt these feedbacks on dopamine signalling, potentially leading to various addictions, including pathological gambling. The goal of this Research Topic is to further our understanding of the neurobiological mechanisms underlying the development of pathological gambling. This eBook contains a cross-disciplinary collection of research and review articles, ranging in scope from animal behavioral models to human imaging studies.

Insomnia and beyond - Exploring the therapeutic potential of orexin receptor antagonists

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193301 Year: Pages: 219 DOI: 10.3389/978-2-88919-330-1 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Therapeutics --- Neurology --- Medicine (General) --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Orexin/hypocretin neuropeptides, produced by a few thousand neurons in the lateral hypothalamus, are of critical importance for the control of vigilance and arousal of vertebrates, from fish to amphibians, birds and mammals. Two orexin peptides, called orexin-A and orexin-B, exist in mammals. They bind with different affinities to two distinct, widely distributed, excitatory G-protein- coupled receptors, orexin receptor type 1 and type 2 (OXR-1/2). The discovery of an OXR mutation causing canine narcolepsy, the narcolepsy-like phenotype of orexin peptide knockout mice, and the orexin neuron loss associated with human narcoleptic patients laid the foundation for the discovery of small molecule OXR antagonists as novel treatments for sleep disorders. Proof of concept studies from Glaxo Smith Kline, Actelion Pharmaceuticals Ltd. and Merck have now consistently demonstrated the efficacy of dual OXR antagonists (DORAs) in promoting sleep in rodents, dogs, non-human primates and humans. Some of these antagonists have completed late stage clinical testing in primary insomnia. Orexin drug discovery programs have also been initiated by other large pharmaceutical companies including Hoffmann La Roche, Novartis, Eli Lilly and Johnson & Johnson. Orexins are increasingly recognized for orchestrating the activity of the organism’s arousal system with appetite, reward and stress processing pathways. Therefore, in addition to models of insomnia, pharmacological effects of DORAs have begun to be investigated in rodent models of addiction, depression and anxiety. The first clinical trials in diabetic neuropathy, migraine and depression have been initiated with Merck’s MK-6096 (www.clinicaltrials.gov). Whereas the pharmacology of DORAs is established for their effects on wakefulness, pharmacological effects of selective OXR-1 or OXR-2 antagonists (SORAs) have remained less clear. From an evolutionary point of view, the OXR-2 was expressed first in most vertebrate lineages, whereas the OXR-1 is believed to result from a gene duplication event, when mammals emerged. Yet, both receptors do not have redundant function. Their brain expression pattern, their intracellular signaling, as well as their affinity for orexin-A and orexin-B differs. During the past decade most preclinical research on selective OXR-1 antagonism was performed with SB-334867. Only in recent years, other selective OXR-1 and OXR-2 antagonists with optimized selectivity profiles and pharmacokinetic properties have been discovered, and phenotypes of OXR-1 and OXR-2 knockout mice were described. The present Research Topic (referred to in the Editorial as “special topics issue”) comprises submissions of original research manuscripts as well as reviews, directed towards the neuropharmacology of OXR antagonists. The submissions are preclinical papers dealing with dual and/or selective OXR antagonists that shed light on the differential contribution of endogenous orexin signaling through both OXRs for cellular, physiological and behavioral processes. Some manuscripts also report on convergence or divergence of DORA vs. SORA effects with phenotypes expressed by OXR-1 or OXR-2 knockout animals. Ultimately these findings may help further define the potential of DORAs and SORAs in particular therapeutic areas in insomnia and beyond insomnia.

Neuronal and glial structural plasticity induced by drugs of abuse

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195985 Year: Pages: 90 DOI: 10.3389/978-2-88919-598-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2016-03-10 08:14:32
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Drugs of abuse induce a host of alterations in brain structure and function, ranging from changes in gene expression and epigenetic processes to aberrant synaptic plasticity to volumetric changes in discrete brain regions. These alterations can be drug class-specific, and are not confined to neurons, as drugs of abuse also induce molecular and cellular alterations in various glial cell types such as astrocytes and microglia. The phenomenon of drug-induced plasticity includes changes in dendritic branching and architecture, dendritic spine density and morphology, astrocyte-neuronal interactions, dysregulation of glutamatergic and GABAergic signaling, and alterations in myelination or microglial phenotype. This drug-induced "rewiring" of the brain at numerous levels can contribute to the development, maintenance, and persistence of the addicted state, as well as associated deficits in normal cognitive functioning. The aim of this Research Topic is to collect recent and important findings related to the structural alterations produced by drug of abuse in neurons, glial, and other cell types of the central nervous system.

Keywords

plasticity --- Dendrite --- Spine --- Glutamate --- Dopamine --- GABA --- Neuron --- glia --- astrocyte --- Addiction

Brain Cholinergic Mechanisms

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197149 Year: Pages: 127 DOI: 10.3389/978-2-88919-714-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Much of our understanding of brain physiology has focused on what one might call, first order processes. These essentially include the primary synaptic mechanisms underlying excitation (mainly glutamate) and inhibition (mainly GABA). Our attention has focused on how the balance of excitation and inhibition regulates the timing, patterns, and extent of information flow across various circuits. A lot less is understood regarding second order processes that sculpt and modify these primary interactions. One such modulatory transmitter in the brain is acetylcholine (ACh). The importance of ACh in modulating various behaviors related to learning, memory, and attention has been recognized over the last four decades as has its involvement in various neurodegenerative and psychiatric disorders. However, our understanding of the mechanistic bases for these actions is at its infancy, at best and much remains to be understood. The array of receptor subtypes for nicotinic and muscarinic receptors, their different locations, and complex signal transduction mechanisms remain a puzzle. Transmitter (ACh) release sites and their relationship to receptor loci are poorly understood. Overall, we lack a unifying framework for conceptualizing how disparate actions of the transmitter on receptors lead to circuit modulation and, eventually, influences on cognition. By its very nature, reports on cholinergic signaling are quite scattered, presented in journals across sub-disciplines and in the context of the systems they modulate. Hence, there is need for consolidation of these studies under a single cover that would allow one to compare and contrast the effects of this transmitter across systems and contexts. This special issue represents one such compilation. The issue addresses cholinergic modulation of defined circuits that lead to specific behaviors and consists of a judicious mixture of review articles and primary papers. The articles focus on three aspects of the system: 1) Cellular targets of cholinergic signaling. 2) Receptor mechanisms. 3) Endogenous transmitter distribution and action. While no common mechanism emerges that can explain cholinergic actions on brain functions, on can postulate that the transmitter system is dynamic, modulating the balance of excitation and inhibition in various circuits. This modulation sets up timed network oscillations and it is tempting to speculate that these oscillations form a template for better encoding of afferent inputs. One can broadly envision the role of the cholinergic system as facilitating processes that allow for more efficient acquisition of learning and engraving of memories. Thus, understanding the mechanisms underlying tonic and stimulus-dependent release of ACh and how it alters firing templates of neuronal networks would be the first step towards elucidating its role in learning and memory. This special topics edition provides clues to some of the actions of ACh. It is hoped that the articles allow the reader to extract common themes and potential mechanisms of cholinergic regulation that will lead to elucidation of general principles governing the actions of this important neuromodulator.

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