Modulation of serotonin and noradrenaline in the BLA by pindolol reduces long-term ethanol intake

Addict Biol. 2019 Jul;24(4):652-663. doi: 10.1111/adb.12630. Epub 2018 Jul 18.

Abstract

Repeated cycles of binge-like alcohol consumption and abstinence change the activity of several neurotransmitter systems. Some of these changes are consolidated following prolonged alcohol use and are thought to play an important role in the development of dependence. We have previously shown that systemic administration of the dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist pindolol selectively reduces long-term but not short-term binge-like consumption of ethanol and alters excitatory postsynaptic currents in basolateral amygdala (BLA) principal neurons. The aim of this study was to investigate the effects of pindolol microinfusions in the BLA on long-term ethanol intake using the drinking-in-the-dark paradigm in mice. We also microinfused RU24969 (5-HT1A/1B receptor partial agonist) and CGP12177 (β1/2 adrenergic antagonist) following long-term ethanol intake and determined the densities of 5-HT1A/1B receptors and β1/2 adrenergic in the BLA following short-term (4 weeks) and long-term ethanol (12 weeks) consumption. We show that intra-BLA infusion of pindolol (1000 pmol/0.5 μl), RU24969 (0.3 and 3 pmol/0.5 μl) and CGP12177 (500 pmol/0.5 μl) produce robust decreases in long-term ethanol consumption. Additionally, we identified reduced β1/2 adrenergic receptor expression and no change in 5-HT1A/1B receptor density in the BLA of long-term ethanol-consuming mice. Collectively, our data highlight the effects of pindolol on voluntary, binge-like ethanol consumption behavior following long-term intake.

Keywords: basolateral amygdala; long term binge-like alcohol; pindolol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Antagonists / pharmacology*
  • Animals
  • Basolateral Nuclear Complex / drug effects*
  • Basolateral Nuclear Complex / metabolism
  • Central Nervous System Depressants / administration & dosage*
  • Central Nervous System Depressants / pharmacology
  • Drug Partial Agonism
  • Ethanol / administration & dosage*
  • Ethanol / pharmacology
  • Humans
  • Indoles / pharmacology
  • Mice
  • Norepinephrine / metabolism
  • Pindolol / pharmacology*
  • Propanolamines / pharmacology
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptor, Serotonin, 5-HT1B / drug effects
  • Receptor, Serotonin, 5-HT1B / metabolism
  • Receptors, Adrenergic, beta-1 / drug effects
  • Receptors, Adrenergic, beta-1 / metabolism
  • Receptors, Adrenergic, beta-2 / drug effects
  • Receptors, Adrenergic, beta-2 / metabolism
  • Serotonin / metabolism
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*

Substances

  • Adrenergic beta-2 Receptor Antagonists
  • Central Nervous System Depressants
  • HTR1B protein, mouse
  • Htr1a protein, mouse
  • Indoles
  • Propanolamines
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole
  • Serotonin
  • Ethanol
  • Pindolol
  • CGP 12177
  • Norepinephrine