Ethanol enhances GABAB-mediated inhibitory postsynaptic transmission on rat midbrain dopaminergic neurons by facilitating GIRK currents

Mauro Federici, Robert Nisticò, Michela Giustizieri, Giorgio Bernardi, Nicola B. Mercuri

Research output: Contribution to journalArticle

Abstract

It is largely accepted that an activation of the dopaminergic system underlies the recreational and convivial effects of ethanol. However, the mechanisms of action of this drug on the dopaminergic neurons are not fully understood yet. In the present study, we have used intracellular electrophysiological techniques (current and single-electrode voltage-clamp) to investigate the actions of ethanol on the -aminobutyric acid (GABA) B-mediated inhibitory postsynaptic potentials (IPSPs) in rat midbrain dopaminergic neurons. Ethanol (10-200 mm) augmented, in a concentration- dependent and reversible manner, the amplitude of the GABAB-IPSP. In addition, the GABAB agonist baclofen generated G-protein-gated inward rectifying K+ channels (GIRK)-related membrane hyperpolarizationsoutward currents that were potentiated by ethanol. The potentiating effect of ethanol persisted in tetrodotoxin (TTX)-treated neurons, suggesting a postsynaptic site of action. These effects of ethanol were not changed by manipulating adenyl cyclase, protein kinases and phospholipase C activity, or by chelating intracellular Ca2+ with EGTA. Interestingly, the outward current caused by the intracytoplasmatic diffusion of the irreversible G-protein activator GTPS was transiently enhanced by ethanol. Our observations suggest that the action of ethanol occurs on activated GIRK channels downstream of the GABAB receptors. These enhancing effects of ethanol on GABAB-induced synaptic responses could modulate alcohol intake and the altered mental and motor performance of individuals in an acute intoxicative phase.

Original languageEnglish
Pages (from-to)1369-1377
Number of pages9
JournalEuropean Journal of Neuroscience
Volume29
Issue number7
DOIs
Publication statusPublished - Apr 2009

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Dopaminergic Neurons
Mesencephalon
GTP-Binding Proteins
Ethanol
Inhibitory Postsynaptic Potentials
Aminobutyrates
Baclofen
Egtazic Acid
Tetrodotoxin
Type C Phospholipases
Ion Channels
Adenylyl Cyclases
gamma-Aminobutyric Acid
Protein Kinase C
Electrodes
Alcohols
Neurons

Keywords

  • Alcohol
  • GABA-IPSP
  • GIRK current
  • Substantia nigra pars compacta
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Ethanol enhances GABAB-mediated inhibitory postsynaptic transmission on rat midbrain dopaminergic neurons by facilitating GIRK currents. / Federici, Mauro; Nisticò, Robert; Giustizieri, Michela; Bernardi, Giorgio; Mercuri, Nicola B.

In: European Journal of Neuroscience, Vol. 29, No. 7, 04.2009, p. 1369-1377.

Research output: Contribution to journalArticle

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