Gamma-hydroxybutyrate and ethanol depress spontaneous excitatory postsynaptic currents in dopaminergic neurons of the substantia nigra

Alfredo Brancucci, Nicola Berretta, Nicola B. Mercuri, Walter Francesconi

Research output: Contribution to journalArticle

Abstract

Gamma-hydroxybutyrate (GHB) has been shown to have therapeutical properties in various psychiatric disorders, especially in alcohol abuse, and to mimic different actions of ethanol at the cellular and system level. Using whole-cell patch-clamp recordings on brain slices of 21- to 25-day-old rats, the present study investigated the effects of GHB and ethanol on spontaneous excitatory postsynaptic currents (sEPSCs) in dopaminergic neurons of the substantia nigra pars compacta (SNc). sEPSCs are an index of glutamate release from the excitatory input to dopamine cells, which play a key role in different reward-related behaviors. We found that GHB and ethanol depressed both the frequency and the amplitude of sEPSCs. These effects were GABA B-independent and the GHB-induced depression was blocked by the GHB receptor antagonist 6,7,8,9-tetrahydro-5[H]benzocyclohepte-5-ol-4-ylidene acetic acid (NCS-382), pointing to a specific effect of this drug. The effects of ethanol were not affected by NCS-382. This study indicates that GHB and ethanol share the effect of reducing the efficacy of excitatory glutamatergic neurotransmission in the SNc by acting through different mechanisms.

Original languageEnglish
Pages (from-to)62-66
Number of pages5
JournalBrain Research
Volume997
Issue number1
DOIs
Publication statusPublished - Jan 30 2004

Keywords

  • Dopaminergic neuron
  • Ethanol
  • Gamma-hydroxybutyric acid
  • NCS-382
  • Spontaneous excitatory postsynaptic current
  • Substantia nigra pars compacta

ASJC Scopus subject areas

  • Neuroscience(all)

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