The galanin receptor-3 antagonist, SNAP 37889, inhibits cue-induced reinstatement of alcohol-seeking and increases c-Fos expression in the nucleus accumbens shell of alcohol-preferring rats

J Psychopharmacol. 2018 Aug;32(8):911-921. doi: 10.1177/0269881118780015. Epub 2018 Jun 21.

Abstract

Introduction: This study aimed to investigate the effects of the galanin-3 receptor antagonist, SNAP 37889, on c-Fos protein expression after cue-induced reinstatement of alcohol-seeking in the brains of alcohol-preferring rats.

Methods: Eighteen alcohol-preferring rats were trained to self-administer 10% v/v ethanol in the presence of response-contingent cues, which was followed by extinction. Rats were then treated with SNAP 37889 (30 mg/kg, i.p.) or vehicle, before being tested for cue-induced reinstatement. Administration of SNAP 37889 reduced cue-induced reinstatement of ethanol-seeking behaviour. To examine the effect of SNAP 37889 and cue-induced reinstatement on neuronal activation, c-Fos expression was measured in subregions of the medial prefrontal cortex and nucleus accumbens.

Results: SNAP 37889 administration increased c-Fos immunoreactivity in the nucleus accumbens shell, but was without effect in the nucleus accumbens core and the medial prefrontal cortex. Dual-label Fos/tyrosine hydroxylase immunohistochemistry was used to examine the effects of SNAP 37889 on dopamine neurons in the ventral tegmental area; however, no differences between SNAP 37889 and vehicle-treated rats were found.

Conclusions: These data support previous findings of galanin-3 receptor involvement in cue-induced reinstatement of alcohol-seeking behaviour, and provide novel evidence that the ability of galanin-3 receptor antagonism to attenuate cue-induced reinstatement relates to activation of the nucleus accumbens shell.

Keywords: Galanin-3 receptor; SNAP 37889; alcohol-preferring rat; immunohistochemistry; operant responding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism / diet therapy*
  • Alcoholism / metabolism
  • Animals
  • Behavior, Animal / drug effects
  • Cues
  • Drug-Seeking Behavior / drug effects*
  • Ethanol
  • Extinction, Psychological / drug effects
  • Indoles / pharmacology*
  • Male
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Receptor, Galanin, Type 3 / antagonists & inhibitors*
  • Self Administration / methods
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism

Substances

  • 1-phenyl-3-((3-(trifluoromethyl)phenyl)imino)-1H-indol-2-one
  • Indoles
  • Proto-Oncogene Proteins c-fos
  • Receptor, Galanin, Type 3
  • Ethanol