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- Title
Ethanol enhances GABA<sub>B</sub>-mediated inhibitory postsynaptic transmission on rat midbrain dopaminergic neurons by facilitating GIRK currents.
- Authors
Federici, Mauro; Nisticò, Robert; Giustizieri, Michela; Bernardi, Giorgio; Mercuri, Nicola B.
- 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 γ-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 hyperpolarizations/outward 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 GTPγS 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.
- Publication
European Journal of Neuroscience, 2009, Vol 29, Issue 7, p1369
- ISSN
0953-816X
- Publication type
Academic Journal
- DOI
10.1111/j.1460-9568.2009.06700.x