Ethanol enhances GABAB‐mediated inhibitory postsynaptic transmission on rat midbrain dopaminergic neurons by facilitating GIRK currents
Copyright policy )Ethanol enhances GABAB‐mediated inhibitory postsynaptic transmission on rat midbrain dopaminergic neurons by facilitating GIRK currents
AbstractIt 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 GABABagonist 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 GABABreceptors. 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.
Male, 571, Patch-Clamp Techniques, Settore BIO/14 - FARMACOLOGIA, Patch-Clamp Technique, Dopamine, Wistar, G Protein-Coupled Inwardly-Rectifying Potassium Channel, Dendrite, In Vitro Techniques, Membrane Potential, Synaptic Transmission, Membrane Potentials, Dose-Response Relationship, Animals; Central Nervous System Depressants; Dendrites; Dopamine; Dose-Response Relationship, Drug; Ethanol; G Protein-Coupled Inwardly-Rectifying Potassium Channels; GABA-B Receptor Agonists; In Vitro Techniques; Inhibitory Postsynaptic Potentials; Male; Membrane Potentials; Mesencephalon; Neurons; Patch-Clamp Techniques; Rats; Rats, Wistar; Receptors, GABA-B; Synapses; Synaptic Transmission, Mesencephalon, Receptors, Inhibitory Postsynaptic Potential, Animals, Rats, Wistar, Neurons, Dose-Response Relationship, Drug, Ethanol, Animal, In Vitro Technique, GABA-B, Central Nervous System Depressants, Dendrites, Neuron, GABA-B Receptor Agonist, Synapse, Animals, Central Nervous System Depressants; pharmacology, Dendrites; drug effects/physiology, Dopamine; metabolism, Dose-Response Relationship; Drug, Ethanol; pharmacology, G Protein-Coupled Inwardly-Rectifying Potassium Channels; metabolism, GABA-B Receptor Agonists, Inhibitory Postsynaptic Potentials; drug effects/physiology, Male, Membrane Potentials; drug effects/physiology, Mesencephalon; drug effects/physiology, Neurons; drug effects/physiology, Patch-Clamp Techniques, Rats, Rats; Wistar, Receptors; GABA-B; metabolism, Synapses; drug effects/physiology, Synaptic Transmission; drug effects/physiology, Rats, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Inhibitory Postsynaptic Potentials, Receptors, GABA-B, GABA-B Receptor Agonists, Central Nervous System Depressant, Synapses, Rat, Drug
Male, 571, Patch-Clamp Techniques, Settore BIO/14 - FARMACOLOGIA, Patch-Clamp Technique, Dopamine, Wistar, G Protein-Coupled Inwardly-Rectifying Potassium Channel, Dendrite, In Vitro Techniques, Membrane Potential, Synaptic Transmission, Membrane Potentials, Dose-Response Relationship, Animals; Central Nervous System Depressants; Dendrites; Dopamine; Dose-Response Relationship, Drug; Ethanol; G Protein-Coupled Inwardly-Rectifying Potassium Channels; GABA-B Receptor Agonists; In Vitro Techniques; Inhibitory Postsynaptic Potentials; Male; Membrane Potentials; Mesencephalon; Neurons; Patch-Clamp Techniques; Rats; Rats, Wistar; Receptors, GABA-B; Synapses; Synaptic Transmission, Mesencephalon, Receptors, Inhibitory Postsynaptic Potential, Animals, Rats, Wistar, Neurons, Dose-Response Relationship, Drug, Ethanol, Animal, In Vitro Technique, GABA-B, Central Nervous System Depressants, Dendrites, Neuron, GABA-B Receptor Agonist, Synapse, Animals, Central Nervous System Depressants; pharmacology, Dendrites; drug effects/physiology, Dopamine; metabolism, Dose-Response Relationship; Drug, Ethanol; pharmacology, G Protein-Coupled Inwardly-Rectifying Potassium Channels; metabolism, GABA-B Receptor Agonists, Inhibitory Postsynaptic Potentials; drug effects/physiology, Male, Membrane Potentials; drug effects/physiology, Mesencephalon; drug effects/physiology, Neurons; drug effects/physiology, Patch-Clamp Techniques, Rats, Rats; Wistar, Receptors; GABA-B; metabolism, Synapses; drug effects/physiology, Synaptic Transmission; drug effects/physiology, Rats, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Inhibitory Postsynaptic Potentials, Receptors, GABA-B, GABA-B Receptor Agonists, Central Nervous System Depressant, Synapses, Rat, Drug
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