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

Behav Brain Res. 2020 May 15:385:112563. doi: 10.1016/j.bbr.2020.112563. Epub 2020 Feb 15.


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.

Keywords: Alcohol use disorder; Binge drinking; Elevated zero maze; Hyperactivity; Locomoter activity; Nucleus accumbens; Operant responding; Reward deficiency.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Binge Drinking / genetics
  • Binge Drinking / metabolism
  • Binge Drinking / physiopathology*
  • Catecholamines / pharmacology*
  • Central Nervous System Depressants / administration & dosage*
  • Conditioning, Operant
  • Dopamine / metabolism
  • Drug-Seeking Behavior / drug effects*
  • Ethanol / administration & dosage*
  • Female
  • Locomotion / drug effects*
  • Male
  • Maze Learning / drug effects
  • Monoamine Oxidase / pharmacology*
  • Neprilysin / pharmacology*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / genetics
  • Reward
  • Self Administration


  • Catecholamines
  • Central Nervous System Depressants
  • DRD2 protein, rat
  • KB220Z
  • RNA, Messenger
  • Receptors, Dopamine D2
  • Ethanol
  • Monoamine Oxidase
  • Neprilysin
  • Dopamine