Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons.
We examined the interaction of ethanol with the gamma-aminobutyric acid (GABA)ergic system in neurons of slices of the rat central amygdala nucleus (CeA), a brain region thought to be critical for the reinforcing effects of ethanol. Brief superfusion of 11-66 mM ethanol significantly increased GABA type A (GABA(A)) receptor-mediated inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in most CeA neurons, with a low apparent EC(50) of 20 mM. Acute superfusion of 44 mM ethanol increased the amplitude of evoked GABA(A) IPSPs and IPSCs in 70% of CeA neurons. The ethanol enhancement of IPSPs and IPSCs occurred to a similar extent in the presence of the GABA type B (GABA(B)) receptor antagonist CGP 55845A, suggesting that this receptor is not involved in the ethanol effect on CeA neurons. Ethanol superfusion also decreased paired-pulse facilitation of evoked GABA(A) IPSPs and IPSCs and always increased the frequency and sometimes the amplitude of spontaneous miniature GABA(A) IPSCs as well as responses to local GABA application, indicating both presynaptic and postsynaptic sites of action for ethanol. Thus, the CeA is the first brain region to reveal, without conditional treatments such as GABA(B) antagonists, consistent, low-dose ethanol enhancement of GABAergic transmission at both pre- and postsynaptic sites. These findings add further support to the contention that the ethanol-GABA interaction in CeA plays an important role in the reinforcing effects of ethanol.
Roberto
Marisa
M
Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Madamba
Samuel G
SG
Moore
Scott D
SD
Tallent
Melanie K
MK
Siggins
George R
GR
D000679:Amygdala / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005071:Evoked Potentials; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000431:Ethanol; D005680:gamma-Aminobutyric Acid