PMID- 32070691 OWN - NLM STAT- MEDLINE DCOM- 20210517 LR - 20210517 IS - 1872-7549 (Electronic) IS - 0166-4328 (Print) IS - 0166-4328 (Linking) VI - 385 DP - 2020 May 15 TI - Administration of a putative pro-dopamine regulator, a neuronutrient, mitigates alcohol intake in alcohol-preferring rats. PG - 112563 LID - S0166-4328(19)31816-9 [pii] LID - 10.1016/j.bbr.2020.112563 [doi] AB - BACKGROUND: Excessive alcohol intake is a serious but preventable public health problem in the United States and worldwide. Alcohol and other substance use disorders occur co-morbid with more generalized reward deficiency disorders, characterized by a reduction in dopamine (DA) signaling within the reward pathway, and classically associated with increased impulsivity, risk taking and subsequent drug seeking behavior. It is postulated that increasing dopamine availability and thus restoring DA homeostasis in the mesocorticolimbic system could reduce the motivation to seek and consume ethanol. Here, we treated animals with a neuro-nutrient, KB220Z also known as Synaptamine, designed to augment DA signaling. METHOD: KB220Z was administered to genetically alcohol-preferring (P) adult male and female rats by oral gavage (PO), intraperioneally (IP), or subcutaneously (SQ) for 4 consecutive days at a 3.4 mL/Kg rat equivalent dose and compared to saline (SQ, IP) or water (PO) controls. Subsequent to treatment, lever pressing and consumption of 10 % ethanol or control 3% sucrose during operant responding was assessed using a drinking in the dark multiple scheduled access (DIDMSA) binge drinking protocol. Locomotor and elevated zero maze activity, and DRD2 mRNA expression via in situ hybridization (ISH) were assessed independently following 4 days of a SQ regimen of KB220Z. RESULTS: KB220Z administered via IP and SQ markedly and immediately reduced binge drinking of 10 % ethanol in both male and female rats whereas PO administration took at least 3 days to decrease lever pressing for ethanol in both male and female rats. There was no effect of SQ KB220Z on 3% sucrose drinking. Elevated activity in the open field was significantly decreased, and time spent in the open arm of the EZM was moderately reduced. The regimen of SQ KB220Z did not impact the number of DRD2 punctae in neurons of the NAc, but the NAc shell expressed more DRD2 mRNA/cell than NAc core independent of KB220Z. CONCLUSION: KB220Z attenuates ethanol drinking and other RDS behaviors in P rats possibly by acting on the dopaminergic system, but not by effecting an increase in NAc DRD2 mRNA expression. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Solanki, Naimesh AU - Solanki N AD - Department of Anatomy, Howard University, Washington D.C., 20059, USA; Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, Washington D.C., 20059, USA. FAU - Abijo, Tomilowo AU - Abijo T AD - Department of Anatomy, Howard University, Washington D.C., 20059, USA; Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, Washington D.C., 20059, USA. FAU - Galvao, Carine AU - Galvao C AD - Department of Anatomy, Howard University, Washington D.C., 20059, USA; Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, Washington D.C., 20059, USA. FAU - Darius, Philippe AU - Darius P AD - Department of Anatomy, Howard University, Washington D.C., 20059, USA; Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, Washington D.C., 20059, USA. FAU - Blum, Kenneth AU - Blum K AD - Western University Health Science Center, Graduate School of Biomedical Sciences, Pomona, CA, 91766 USA; Institute of Psychology, ELTE Eotvos Lorand University, Budapest, Hungary. FAU - Gondre-Lewis, Marjorie C AU - Gondre-Lewis MC AD - Department of Anatomy, Howard University, Washington D.C., 20059, USA; Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, Washington D.C., 20059, USA. Electronic address: mgondre-lewis@howard.edu. LA - eng GR - R01 AA021262/AA/NIAAA NIH HHS/United States GR - R41 MD012318/MD/NIMHD NIH HHS/United States GR - U54 HD090257/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200215 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Catecholamines) RN - 0 (Central Nervous System Depressants) RN - 0 (DRD2 protein, rat) RN - 0 (KB220Z) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Dopamine D2) RN - 3K9958V90M (Ethanol) RN - EC 1.4.3.4 (Monoamine Oxidase) RN - EC 3.4.24.11 (Neprilysin) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Behavior, Animal/*drug effects MH - Binge Drinking/genetics/metabolism/*physiopathology MH - Catecholamines/*pharmacology MH - Central Nervous System Depressants/*administration & dosage MH - Conditioning, Operant MH - Dopamine/metabolism MH - Drug-Seeking Behavior/*drug effects MH - Ethanol/*administration & dosage MH - Female MH - Locomotion/*drug effects MH - Male MH - Maze Learning/drug effects MH - Monoamine Oxidase/*pharmacology MH - Neprilysin/*pharmacology MH - RNA, Messenger/drug effects/metabolism MH - Rats MH - Receptors, Dopamine D2/*drug effects/genetics MH - Reward MH - Self Administration PMC - PMC7244251 MID - NIHMS1572729 OTO - NOTNLM OT - Alcohol use disorder OT - Binge drinking OT - Elevated zero maze OT - Hyperactivity OT - Locomoter activity OT - Nucleus accumbens OT - Operant responding OT - Reward deficiency COIS- Declaration of Competing Interest Kenneth Blum owns stock in some companies holding patents on genetic testing and KB220PAM. MGL serves on the Scientific Advisory Board of Geneus Health, which at the submission of this manuscript holds all rights to KB220Z. NS, TA, CG and PD have no other conflicts of interest to declare. EDAT- 2020/02/20 06:00 MHDA- 2021/05/18 06:00 PMCR- 2021/05/15 CRDT- 2020/02/20 06:00 PHST- 2019/12/13 00:00 [received] PHST- 2020/02/13 00:00 [revised] PHST- 2020/02/14 00:00 [accepted] PHST- 2020/02/20 06:00 [pubmed] PHST- 2021/05/18 06:00 [medline] PHST- 2020/02/20 06:00 [entrez] PHST- 2021/05/15 00:00 [pmc-release] AID - S0166-4328(19)31816-9 [pii] AID - 10.1016/j.bbr.2020.112563 [doi] PST - ppublish SO - Behav Brain Res. 2020 May 15;385:112563. doi: 10.1016/j.bbr.2020.112563. Epub 2020 Feb 15.