Involvement of non-NMDA glutamate receptors in central amygdala in synaptic actions of ethanol and ethanol-induced reward behavior.
The central nucleus of the amygdala (CeA) plays a critical role in positive emotional responses that involve stimulus-reward learning and are induced by the reinforcing effects of many drugs of abuse, including alcohol. Behavioral studies have implicated CeA as a key brain structure in alcohol reward, but the underlying mechanisms are still poorly understood. Recent studies have demonstrated that both NMDA and non-NMDA receptors in CeA neurons are targets of acute and chronic alcohol in naive and alcohol-dependent animals. However, little is known about the role of CeA non-NMDA receptors in synaptic actions of alcohol and, particularly, in the behavior of alcohol reward. In the present study with both whole-cell voltage-clamp recordings in CeA slices in vitro and analysis of an animal model of conditioned place preference (CPP) in vivo, we investigated the synaptic mechanisms for actions of acute and chronic ethanol on CeA non-NMDA receptor functions and their contribution to ethanol-induced reward behavior. Acute ethanol significantly inhibited evoked and miniature synaptic currents mediated by non-NMDA receptors through inhibitions of both postsynaptic non-NMDA receptors and presynaptic glutamate release involving N-type Ca2+ channels. CeA neurons from rats exhibiting the ethanol-induced CPP behavior showed a significant increase in non-NMDA synaptic transmission. Blockade of this increased synaptic transmission through CeA microinjection abolished the CPP behavior. These results suggest that acute alcohol inhibits CeA non-NMDA synaptic transmission through both presynaptic and postsynaptic mechanisms, and chronic alcohol upregulates this synaptic activity, which is required for the alcohol-induced reward behavior.
Zhu
Wei
W
Department of Anesthesiology and Pain Medicine, The University of Texas-MD Anderson Cancer Center, Houston, Texas 77030, USA.
Bie
Bihua
B
Pan
Zhizhong Z
ZZ
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012201:Reward; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol