Bupropion, a possible antidepressant without negative effects on alcohol relapse

Eur Neuropsychopharmacol. 2019 Jun;29(6):756-765. doi: 10.1016/j.euroneuro.2019.03.012. Epub 2019 May 4.

Abstract

Rationale: the role that antidepressants play on alcohol consumption is not well understood. Previous studies have reported that treatment with a Selective Serotonin Reuptake Inhibitor (SSRIs) increases alcohol consumption in an animal model of relapse, however it is unknown whether this effect holds for other antidepressants such as the atypical dopamine/norepinephrine reuptake inhibitors (SNDRI).

Objectives: the main goal of the present study was to compare the effects of two classes of antidepressants drugs, bupropion (SNDRI) and fluoxetine (SSRI), on alcohol consumption during relapse. Since glutamatergic and endocannabinoid signaling systems plays an important role in alcohol abuse and relapse, we also evaluated the effects of both antidepressants onthe expression of the main important genes and proteins of both systems in the prefrontal cortex, a critical brain region in alcohol relapse.

Methods: rats were trained to self-administered alcohol. During abstinence, rats received a 14d-treatment with vehicle, fluoxetine (10 mg/kg) or bupropion (20 mg/kg), and we evaluated alcohol consumption during relapse for 3 weeks. Samples of prefrontal cortex were taken to evaluate the mRNA and protein expression of the different components of glutamatergic and endocannabinoid signaling systems.

Results: fluoxetine treatment induced a long-lasting increase in alcohol consumption during relapse, an effect that was not observed in the case of bupropion treatment. The observed increases in alcohol consumption were accompanied by distinct alterations in the glutamate and endocannabinoid systems.

Conclusions: our results suggest that SSRIs can negatively impact alcohol consumption in relapse while SNDRIs have no effects. The observed increase in alcohol consumption are accompanied by functional alterations in the glutamatergic and endocannabinoid systems. This finding could open new strategies for the treatment of depression in patients with alcohol use disorders.

Keywords: Alcohol; Antidepressant; Cannabinoid; Glutamate; Prefrontal cortex; Relapse.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alcohol Drinking
  • Alcoholism / drug therapy*
  • Alcoholism / psychology
  • Animals
  • Antidepressive Agents, Second-Generation / adverse effects*
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Bupropion / adverse effects*
  • Bupropion / therapeutic use*
  • Dopamine Uptake Inhibitors / adverse effects*
  • Dopamine Uptake Inhibitors / therapeutic use*
  • Endocannabinoids / metabolism
  • Fluoxetine / therapeutic use
  • Male
  • Prefrontal Cortex / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Receptors, Glutamate / biosynthesis
  • Receptors, Glutamate / genetics
  • Recurrence
  • Selective Serotonin Reuptake Inhibitors / therapeutic use

Substances

  • Antidepressive Agents, Second-Generation
  • Dopamine Uptake Inhibitors
  • Endocannabinoids
  • RNA, Messenger
  • Receptors, Glutamate
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Bupropion