SNARE Complex-Associated Proteins in the Lateral Amygdala of Macaca mulatta Following Long-Term Ethanol Drinking

Alcohol Clin Exp Res. 2018 Sep;42(9):1661-1673. doi: 10.1111/acer.13821. Epub 2018 Jul 15.


Background: Recent work with long-term ethanol (EtOH) self-administration in nonhuman primate models has revealed a complex array of behavioral and physiological effects that closely mimic human alcohol abuse. Detailed neurophysiological analysis in these models suggests a myriad of pre- and postsynaptic neurobiological effects that may contribute to the behavioral manifestations of long-term EtOH drinking. The molecular mechanisms regulating presynaptic effects of this chronic EtOH exposure are largely unknown. To this end, we analyzed the effects of long-term EtOH self-administration on the levels of presynaptic SNARE complex proteins in Macaca mulatta basolateral amygdala, a brain region known to regulate both aversive and reward-seeking behaviors.

Methods: Basolateral amygdala samples from control and EtOH-drinking male and female monkeys were processed. Total basolateral amygdala protein was analyzed by Western blotting using antibodies directed against both core SNARE and SNARE-associated proteins. We also performed correlational analyses between protein expression levels and a number of EtOH drinking parameters, including lifetime grams of EtOH consumed, preference, and blood alcohol concentration.

Results: Significant interactions or main effects of sex/drinking were seen for a number of SNARE core and SNARE-associated proteins. Across the range of EtOH-drinking phenotypes, SNAP25 and Munc13-1 proteins levels were significantly different between males and females, and Munc13-2 levels were significantly lower in animals with a history of EtOH drinking. A separate analysis of very heavy-drinking individuals revealed significant decreases in Rab3c (females) and complexin 2 (males).

Conclusions: Protein expression analysis of basolateral amygdala total protein from controls and animals following long-term EtOH self-administration suggests a number of alterations in core SNARE or SNARE-associated components that could dramatically alter presynaptic function. A number of proteins or multiprotein components were also correlated with EtOH drinking behavior, which suggest a potentially heritable role for presynaptic SNARE proteins.

Keywords: Complexin 1/2; Macaque; Munc13-1/2; Munc18-1; Rab3a/c.

Publication types

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

MeSH terms

  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / metabolism*
  • Alcohol Drinking / trends*
  • Animals
  • Basolateral Nuclear Complex / chemistry
  • Basolateral Nuclear Complex / drug effects*
  • Basolateral Nuclear Complex / metabolism*
  • Ethanol / administration & dosage*
  • Ethanol / adverse effects
  • Female
  • Macaca mulatta
  • Male
  • SNARE Proteins / analysis
  • SNARE Proteins / biosynthesis*
  • Self Administration
  • Time Factors


  • SNARE Proteins
  • Ethanol