title: Gamma-hydroxybutyrate and ethanol depress spontaneous excitatory postsynaptic currents in dopaminergic neurons of the substantia nigra.
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.
authors.affiliation: Dipartimento di Fisiologia e Biochimica G. Moruzzi, Università di Pisa, Pisa, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Brancucci
authors.forename: Nicola
authors.initials: N
authors.lastname: Berretta
authors.forename: Nicola B
authors.initials: NB
authors.lastname: Mercuri
authors.forename: Walter
authors.initials: W
authors.lastname: Francesconi
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology; D001567:Benzocycloheptenes / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012978:Sodium Oxybate / Q000494:pharmacology*; D013378:Substantia Nigra / Q000166:cytology* / Q000187:drug effects
chemical_list: D000759:Adjuvants, Anesthesia; D000927:Anticonvulsants; D001567:Benzocycloheptenes; D002492:Central Nervous System Depressants; C066471:NCS 382; D000431:Ethanol; D012978:Sodium Oxybate; D004298:Dopamine