Administration of a putative pro-dopamine regulator, a neuronutrient, mitigates alcohol intake in alcohol-preferring rats.

Autor: Solanki N; Department of Anatomy, Howard University, Washington D.C., 20059, USA; Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, Washington D.C., 20059, USA., Abijo T; Department of Anatomy, Howard University, Washington D.C., 20059, USA; Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, Washington D.C., 20059, USA., Galvao C; Department of Anatomy, Howard University, Washington D.C., 20059, USA; Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, Washington D.C., 20059, USA., Darius P; Department of Anatomy, Howard University, Washington D.C., 20059, USA; Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, Washington D.C., 20059, USA., Blum K; Western University Health Science Center, Graduate School of Biomedical Sciences, Pomona, CA, 91766 USA; Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary., Gondré-Lewis MC; 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.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2020 May 15; Vol. 385, pp. 112563. Date of Electronic Publication: 2020 Feb 15.
DOI: 10.1016/j.bbr.2020.112563
Abstrakt: 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.
Competing Interests: 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.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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