20
views
0
recommends
+1 Recommend
1 collections
    0
    shares

      To submit to Bentham Journals, please click here

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Common Neurogenetic Diagnosis and Meso-Limbic Manipulation of Hypodopaminergic Function in Reward Deficiency Syndrome (RDS): Changing the Recovery Landscape

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Abstract: Background: In 1990, Blum and associates provided the first confirmed genetic link between the DRD2 polymorphisms and alcoholism. This finding was based on an earlier conceptual framework, which served as a blueprint for their seminal genetic association discovery they termed “Brain Reward Cascade.” These findings were followed by a new way of understanding all addictive behaviors (substance and non-substance) termed “Reward Deficiency Syndrome” (RDS). RDS incorporates a complex multifaceted array of inheritable behaviors that are polygenic.

          Objective: In this review article, we attempt to clarify these terms and provide a working model to accurately diagnose and treat these unwanted behaviors.

          Method: We are hereby proposing the development of a translational model we term “Reward Deficiency Solution System™” that incorporates neurogenetic testing and meso-limbic manipulation of a “hypodopaminergic” trait/state, which provides dopamine agonistic therapy (DAT) as well as reduced “dopamine resistance,” while embracing “dopamine homeostasis.”

          Result: The result is better recovery and relapse prevention, despite DNA antecedents, which could impact the recovery process and relapse. Understanding the commonality of mental illness will transform erroneous labeling based on symptomatology, into a genetic and anatomical etiology. WC: 184.

          Related collections

          Most cited references80

          • Record: found
          • Abstract: found
          • Article: not found

          Addiction-like reward dysfunction and compulsive eating in obese rats: Role for dopamine D2 receptors

          We found that development of obesity was coupled with the emergence of a progressively worsening brain reward deficit. Similar changes in reward homeostasis induced by cocaine or heroin is considered a critical trigger in the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2R) were downregulated in obese rats, similar to previous reports in human drug addicts. Moreover, lentivirus-mediated knockdown of striatal D2R rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuitries and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward.

            The nucleus accumbens is a key mediator of cocaine reward, but the distinct roles of the two subpopulations of nucleus accumbens projection neurons, those expressing dopamine D1 versus D2 receptors, are poorly understood. We show that deletion of TrkB, the brain-derived neurotrophic factor (BDNF) receptor, selectively from D1+ or D2+ neurons oppositely affects cocaine reward. Because loss of TrkB in D2+ neurons increases their neuronal excitability, we next used optogenetic tools to control selectively the firing rate of D1+ and D2+ nucleus accumbens neurons and studied consequent effects on cocaine reward. Activation of D2+ neurons, mimicking the loss of TrkB, suppresses cocaine reward, with opposite effects induced by activation of D1+ neurons. These results provide insight into the molecular control of D1+ and D2+ neuronal activity as well as the circuit-level contribution of these cell types to cocaine reward.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior.

              In the basal ganglia, convergent input and dopaminergic modulation of the direct striatonigral and the indirect striatopallidal pathways are critical in rewarding and aversive learning and drug addiction. To explore how the basal ganglia information is processed and integrated through these two pathways, we developed a reversible neurotransmission blocking technique, in which transmission of each pathway was selectively blocked by specific expression of transmission-blocking tetanus toxin in a doxycycline-dependent manner. The results indicated that the coordinated modulation of these two pathways was necessary for dopamine-mediated acute psychostimulant actions. This modulation, however, shifted to the predominant roles of the direct pathway in reward learning and cocaine sensitization and the indirect pathway in aversive behavior. These two pathways thus have distinct roles: the direct pathway critical for distinguishing associative rewarding stimuli from nonassociative ones and the indirect pathway for rapid memory formation to avoid aversive stimuli.
                Bookmark

                Author and article information

                Journal
                Curr Neuropharmacol
                Curr Neuropharmacol
                CN
                Current Neuropharmacology
                Bentham Science Publishers
                1570-159X
                1875-6190
                January 2017
                January 2017
                : 15
                : 1
                : 184-194
                Affiliations
                [1 ]Department of Psychiatry, University of Florida College of Medicine and McKnight Brain Institute, Gainesville, FL, USA;
                [2 ]Department of Psychiatry, University of Vermont, Burlington, VT, USA;
                [3 ]Division of Neuroscience Based Therapy, Summit Estates Recovery Center, Las Gatos, CA, USA;
                [4 ]Dominion Diagnostics, LLC, North Kingstown, RI, USA;
                [5 ]IGENE, LLC, Austin, TX, USA;
                [6 ]Department of Nutrigenomics, RDSolutions, Inc., Salt Lake City, UT, USA;
                [7 ]Division of Neuroimaging, Department of Psychiatry, University of Minnesota College of Medicine, Minneapolis, MN, USA;
                [8 ]Department of Psychology, Eotvos Lorand University, Budapest, Hungary;
                [9 ]Department of Psychology, University of Gothenburg, Göteborg, Sweden;
                [10 ]Departments of Psychiatry and Anatomy & Neurobiology, Boston University School of Medicine and Boston VA Healthcare System, Boston, MA, USA;
                [11 ]PATH Foundation NY, New York, NY, USA;
                Departments of Psychiatry & Behavioral Sciences , Keck School of Medicine of USC, Los Angeles, CA, USA; Department of Psychiatry, Washington University School of Medicine. St. Louis, MO, USA;
                [14 ]Division of Neuroscience Research and Addiction Therapy, The Shores Treatment and Recovery, Port Saint Lucie, FL, USA
                Author notes
                [* ]Address correspondence to this author at the Department of Psychiatry & McKnight Brain Institute, University of Florida, College of Medicine, Box 100183 Gainesville, FL, USA 32610-0183; Tel: 352-392-6680; Fax: 352-392-8217; E-mail: drd2gene@ 123456ufl.edu
                Article
                CN-15-184
                10.2174/1570159X13666160512150918
                5327445
                27174576
                6fefdc23-a520-4127-a401-d9a3f0b1b915
                ©Febo 2017 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                dopamine homeostasis,genetics,reward deficiency solution system,reward deficiency syndrome (rds)

                Comments

                Comment on this article