TY - JOUR
T1 - Gamma-hydroxybutyrate and ethanol depress spontaneous excitatory postsynaptic currents in dopaminergic neurons of the substantia nigra
AU - Brancucci, Alfredo
AU - Berretta, Nicola
AU - Mercuri, Nicola B.
AU - Francesconi, Walter
PY - 2004/1/30
Y1 - 2004/1/30
N2 - 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.
AB - 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.
KW - Dopaminergic neuron
KW - Ethanol
KW - Gamma-hydroxybutyric acid
KW - NCS-382
KW - Spontaneous excitatory postsynaptic current
KW - Substantia nigra pars compacta
UR - http://www.scopus.com/inward/record.url?scp=0346725075&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0346725075&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2003.10.046
DO - 10.1016/j.brainres.2003.10.046
M3 - Article
C2 - 14715150
AN - SCOPUS:0346725075
VL - 997
SP - 62
EP - 66
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -