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      A Genetic Model of Impulsivity, Vulnerability to Drug Abuse and Schizophrenia-Relevant Symptoms With Translational Potential: The Roman High- vs. Low-Avoidance Rats

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          Abstract

          The bidirectional selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for respectively rapid vs. poor acquisition of active avoidant behavior has generated two lines/strains that differ markedly in terms of emotional reactivity, with RHA rats being less fearful than their RLA counterparts. Many other behavioral traits have been segregated along the selection procedure; thus, compared with their RLA counterparts, RHA rats behave as proactive copers in the face of aversive conditions, display a robust sensation/novelty seeking (SNS) profile, and show high impulsivity and an innate preference for natural and drug rewards. Impulsivity is a multifaceted behavioral trait and is generally defined as a tendency to express actions that are poorly conceived, premature, highly risky or inappropriate to the situation, that frequently lead to unpleasant consequences. High levels of impulsivity are associated with several neuropsychiatric conditions including attention-deficit hyperactivity disorder, obsessive-compulsive disorder, schizophrenia, and drug addiction. Herein, we review the behavioral and neurochemical differences between RHA and RLA rats and survey evidence that RHA rats represent a valid genetic model, with face, construct, and predictive validity, to investigate the neural underpinnings of behavioral disinhibition, novelty seeking, impulsivity, vulnerability to drug addiction as well as deficits in attentional processes, cognitive impairments and other schizophrenia-relevant traits.

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          Depression: a new animal model sensitive to antidepressant treatments.

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            Cortical inhibitory neurons and schizophrenia.

            Impairments in certain cognitive functions, such as working memory, are core features of schizophrenia. Convergent findings indicate that a deficiency in signalling through the TrkB neurotrophin receptor leads to reduced GABA (gamma-aminobutyric acid) synthesis in the parvalbumin-containing subpopulation of inhibitory GABA neurons in the dorsolateral prefrontal cortex of individuals with schizophrenia. Despite both pre- and postsynaptic compensatory responses, the resulting alteration in perisomatic inhibition of pyramidal neurons contributes to a diminished capacity for the gamma-frequency synchronized neuronal activity that is required for working memory function. These findings reveal specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.
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              Drug Addiction: Updating Actions to Habits to Compulsions Ten Years On.

              A decade ago, we hypothesized that drug addiction can be viewed as a transition from voluntary, recreational drug use to compulsive drug-seeking habits, neurally underpinned by a transition from prefrontal cortical to striatal control over drug seeking and taking as well as a progression from the ventral to the dorsal striatum. Here, in the light of burgeoning, supportive evidence, we reconsider and elaborate this hypothesis, in particular the refinements in our understanding of ventral and dorsal striatal mechanisms underlying goal-directed and habitual drug seeking, the influence of drug-associated Pavlovian-conditioned stimuli on drug seeking and relapse, and evidence for impairments in top-down prefrontal cortical inhibitory control over this behavior. We further review animal and human studies that have begun to define etiological factors and individual differences in the propensity to become addicted to drugs, leading to the description of addiction endophenotypes, especially for cocaine addiction. We consider the prospect of novel treatments for addiction that promote abstinence from and relapse to drug use.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                05 July 2019
                2019
                : 13
                : 145
                Affiliations
                [1] 1Department of Life and Environmental Sciences, University of Cagliari , Cagliari, Italy
                [2] 2Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, School of Medicine, Institute of Neurosciences, Universitat Autónoma de Barcelona , Barcelona, Spain
                Author notes

                Edited by: Margarita Moreno, University of Almería, Spain

                Reviewed by: Almira Vazdarjanova, Augusta University, United States; Marta Miquel, University of Jaume I, Spain

                *Correspondence: Osvaldo Giorgi giorgi@ 123456unica.it Alberto Fernández-Teruel albert.fernandez.teruel@ 123456uab.cat
                Article
                10.3389/fnbeh.2019.00145
                6624787
                31333426
                5ac3e0a3-0fec-46bf-af2e-154e13bd1cea
                Copyright © 2019 Giorgi, Corda and Fernández-Teruel.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 January 2019
                : 18 June 2019
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 188, Pages: 16, Words: 14809
                Categories
                Neuroscience
                Review

                Neurosciences
                roman high- and low-avoidance rats,genetic animal model,impulsivity,schizophrenia-relevant symptoms,sensation/novelty seeking,vulnerability to drug abuse,mesoaccumbens and mesocortical dopaminergic pathways

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