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dc.contributor.authorBlum, Kennethen_US
dc.contributor.authorChen, Amanda Lih Chuanen_US
dc.contributor.authorChen, Thomas J. H.en_US
dc.contributor.authorBraverman, Eric R.en_US
dc.contributor.authorReinking, Jeffreyen_US
dc.contributor.authorBlum, Seth H.en_US
dc.contributor.authorCassel, Kimberlyen_US
dc.contributor.authorDowns, Bernard W.en_US
dc.contributor.authorWaite, Roger L.en_US
dc.contributor.authorWilliams, Lonnaen_US
dc.contributor.authorPrihoda, Thomas J.en_US
dc.contributor.authorKerner, Mallory M.en_US
dc.contributor.authorPalomo, Tomasen_US
dc.contributor.authorComings, David E.en_US
dc.contributor.authorTung, Howarden_US
dc.contributor.authorRhoades, Patricken_US
dc.contributor.authorOscar-Berman, Marleneen_US
dc.date.accessioned2012-01-11T21:09:09Z
dc.date.available2012-01-11T21:09:09Z
dc.date.copyright2008
dc.date.issued2008-11-12
dc.identifier.citationBlum, Kenneth, Amanda Lih Chuan Chen, Thomas JH Chen, Eric R Braverman, Jeffrey Reinking, Seth H Blum, Kimberly Cassel, Bernard W Downs, Roger L Waite, Lonna Williams, Thomas J Prihoda, Mallory M Kerner, Tomas Palomo, David E Comings, Howard Tung, Patrick Rhoades, Marlene Oscar-Berman. "Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary" Theoretical Biology & Medical Modelling 5:24. (2008)
dc.identifier.issn1742-4682
dc.identifier.urihttps://hdl.handle.net/2144/3189
dc.description.abstractBACKGROUND AND HYPOTHESIS. Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of D2 receptors. PROPOSAL AND CONCLUSION. The authors propose that D2 receptor stimulation can be accomplished via the use of Synapatmine™, a natural but therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model has been proven in research showing DNA-directed compensatory overexpression (a form of gene therapy) of the DRD2 receptors, resulting in a significant reduction in alcohol craving behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger in the meso-limbic DA system.en_US
dc.description.sponsorshipLifeGen, Inc.; Electronic Waveform Lab; Huntington Beach and Path Research Foundationen_US
dc.language.isoen
dc.publisherBioMed Centralen_US
dc.rightsCopyright 2008 Blum et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0
dc.titleActivation instead of Blocking Mesolimbic Dopaminergic Reward Circuitry Is a Preferred Modality in the Long Term Treatment of Reward Deficiency Syndrome (RDS): A Commentaryen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/1742-4682-5-24
dc.identifier.pmid19014506
dc.identifier.pmcid2615745


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Copyright 2008 Blum et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright 2008 Blum et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.