Involvement of Non-NMDA Glutamate Receptors in Central Amygdala in Synaptic Actions of Ethanol and Ethanol-Induced Reward Behavior

Zhu, Wei; Bie, Bihua; Pan, Zhizhong Z.

doi:10.1523/jneurosci.3912-06.2007

Cited by 63 publications

(93 citation statements)

References 60 publications

(93 reference statements)

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“…This intriguing possibility will be examined in future studies. Recent studies have suggested a presynaptic contribution to ethanol's actions on NMDAEPSCs in some brain regions, including the ethanoldependent rat CeA (Roberto et al, 2004) as well as the ethanol naive rat CeA (Zhu et al, 2007). In the vBNST, we found that ethanol did not inhibit AMPA-EPSCs, yet inhibits currents elicited by exogenous application of NMDA; suggesting that ethanol acts solely via a postsynaptic mechanism to inhibit NMDA-EPSCs.…”

Section: Ethanol Inhibits Nmda-epscs In Vbnst Through a Postsynaptic mentioning

confidence: 43%

“…While the bulk of the literature demonstrates that ethanol inhibits NMDAR function via a postsynaptic mechanism, several recent studies in the nucleus accumbens and central nucleus of the amygdala (CeA) suggest a presynaptic component (Hendricson et al, 2004;Zhang et al, 2005;Zhu et al, 2007). In order to evaluate the effect of ethanol on presynaptic function at glutamatergic synapses in the vBNST, we examined the ability of ethanol to inhibit AMPA receptor-mediated synaptic transmission.…”

Section: Ethanol Inhibits Nmda-epscs In the Vbnst Through A Postsynapmentioning

confidence: 99%

“…The study of the precise mechanisms of ethanol inhibition of NMDARs has provided mixed results as well. While much of the literature supports a postsynaptic mechanism (Lovinger et al, 1989) for ethanol inhibition of NMDA-excitatory postsynaptic currents (EPSCs), recent studies in brain slices have suggested an additional presynaptic component (Hendricson et al, 2004;Zhang et al, 2005;Zhu et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Alcohol Inhibits NR2B-Containing NMDA Receptors in the Ventral Bed Nucleus of the Stria Terminalis

Kash

Matthews

Winder

2007

Neuropsychopharmacol

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Components of the mesolimbic dopamine system, in particular dopaminergic cells in the ventral tegmental area (VTA), have been implicated in the acute reinforcing actions of ethanol. The ventral bed nucleus of the stria terminalis (vBNST) potently regulates dopaminergic cell firing in the VTA, and has been implicated in the behavioral actions of ethanol. The N-methyl-D-asparate receptor (NMDAR) is a major molecular target of ethanol, however, current evidence suggests that ethanol regulation of NMDAR function is widely variable and likely depends on a number of factors. Thus, it is critical to investigate ethanol regulation of NMDAR function at synapses relevant to ethanol-regulated behaviors, such as in the vBNST. Here we show, using multiple techniques, that ethanol inhibits NMDAR function in vBNST neurons in a postsynaptic fashion. Further, we demonstrate the functional presence of both NR2A and NR2B-containing NMDARs in the vBNST. While genetic removal of NR2A did not alter the magnitude of ethanol inhibition, pharmacological blockade of NR2B rendered synaptically activated NMDARs insensitive to ethanol inhibition. Finally, we demonstrate that ethanol inhibits NMDARs in cells in the vBNST that project to the VTA, providing a direct means by which ethanol in the vBNST can modulate the dopaminergic system.

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Section: Ethanol Inhibits Nmda-epscs In Vbnst Through a Postsynaptic mentioning

confidence: 43%

Section: Ethanol Inhibits Nmda-epscs In the Vbnst Through A Postsynapmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alcohol Inhibits NR2B-Containing NMDA Receptors in the Ventral Bed Nucleus of the Stria Terminalis

Kash

Matthews

Winder

2007

Neuropsychopharmacol

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“…In addition, recombinant AMPA receptors containing GluRs 2 and 3 exhibit slightly decreased EtOH sensitivity in comparison to those containing GluRs1, 2, and 3 or 3 alone (Akinshola et al 2003). Recent studies suggest that this EtOH action involves increased receptor desensitization (Möykkynen et al 2003(Möykkynen et al , 2009, and thus the drug has little impact on AMPAR-mediated synaptic responses at most synapses given that desensitization does not contribute to the amplitude or time course of excitatory postsynaptic currents (EPSCs) Ariwodola et al 2003, but see Nie et al 1993Nie et al , 1994Roberto et al 2004b;Mameli et al 2005;Zhu et al 2007). …”

Section: Ligand-gated Ion Channels and Postsynaptic Ethanol Effectsmentioning

confidence: 99%

“…Indeed, there is mounting evidence that changes in the cystine/glutamate exchanger generate increases in extracellular glutamate produced by some drugs of abuse (Kalivas 2009). Evidence of increased synaptic glutamate release has been observed in amygdala following chronic EtOH treatment (Lack et al 2007;Zhu et al 2007;Roberto et al 2004b). Decreases in glutamate uptake have also been noted following chronic EtOH exposure (Melendez et al 2005).…”

Section: Chronic Ethanol Effects On Glutamatergic Transmission and Glmentioning

confidence: 99%

Synaptic Effects Induced by Alcohol

Lovinger

Roberto

2010

Current Topics in Behavioral Neurosciences

117

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Ethanol (EtOH) has effects on numerous cellular molecular targets, and alterations in synaptic function are prominent among these effects. Acute exposure to EtOH activates or inhibits the function of proteins involved in synaptic transmission, while chronic exposure often produces opposing and/or compensatory/homeostatic effects on the expression, localization, and function of these proteins. Interactions between different neurotransmitters (e.g., neuropeptide effects on release of small molecule transmitters) can also influence both acute and chronic EtOH actions. Studies in intact animals indicate that the proteins affected by EtOH also play roles in the neural actions of the drug, including acute intoxication, tolerance, dependence, and the seeking and drinking of EtOH. This chapter reviews the literature describing these acute and chronic synaptic effects of EtOH and their relevance for synaptic transmission, plasticity, and behavior. KeywordsGABA; Glutamate; Monoamine; Neuropeptide; Neurotransmitter receptor; Presynaptic; Postsynaptic; Protein phosphorylation; Synaptic plasticity; Intoxication; Tolerance; Dependence Acute Ethanol ActionsEthanol (EtOH) produces intoxication through actions on the central nervous system (CNS) at concentrations ranging from low to ~100 mM (at least in non-tolerant humans and experimental animals). A number of proteins involved in synaptic transmission are altered by EtOH effects within this concentration range. The target proteins include, but are not limited to, ion channels, neurotransmitter receptors, and intracellular signaling proteins. The first section of this article will review the literature describing the most prominent acute EtOH effects on synaptic transmission in the CNS. This review is not meant to be comprehensive, but rather to cover those effects that have been observed most consistently and are thought to contribute to intoxication.

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Presynaptic Ethanol Actions: Potential Roles in Ethanol Seeking

Lovinger

2017

The Neuropharmacology of Alcohol

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Ethanol produces intoxication through actions on numerous molecular and cellular targets. Adaptations involving these and other targets contribute to chronic drug actions that underlie continued and problematic drinking. Among the mechanisms involved in these ethanol actions are alterations in presynaptic mechanisms of synaptic transmission, including presynaptic protein function and excitation-secretion coupling. At synapses in the central nervous system (CNS), excitation-secretion coupling involves ion channel activation followed by vesicle fusion and neurotransmitter release. These mechanisms are altered by presynaptic neurotransmitter receptors and prominently by G protein-coupled receptors (GPCRs). Studies over the last 20-25 years have revealed that acute ethanol exposure alters neurotransmitter secretion, with especially robust effects on synapses that use the neurotransmitter gamma-aminobutyric acid (GABA). Intracellular signaling pathways involving second messengers such as cyclic AMP and calcium are implicated in these acute ethanol actions. Ethanol-induced release of neuropeptides and small molecule neurotransmitters that act on presynaptic GPCRs also contribute to presynaptic potentiation at synapses in the amygdala and hippocampus and inhibition of GABA release in the striatum. Prolonged exposure to ethanol alters neurotransmitter release at many CNS GABAergic and glutamatergic synapses, and changes in GPCR function are implicated in many of these neuroadaptations. These presynaptic neuroadaptations appear to involve compensation for acute drug effects at some synapses, but "allostatic" effects that result in long-term resetting of synaptic efficacy occur at others. Current investigations are determining how presynaptic neuroadaptations contribute to behavioral changes at different stages of alcohol drinking, with increasing focus on circuit adaptations underlying these behaviors. This chapter will discuss the acute and chronic presynaptic effects of ethanol in the CNS, as well as some of the consequences of these effects in amygdala and corticostriatal circuits that are related to excessive seeking/drinking and ethanol abuse.

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Involvement of Non-NMDA Glutamate Receptors in Central Amygdala in Synaptic Actions of Ethanol and Ethanol-Induced Reward Behavior

Cited by 63 publications

References 60 publications

Alcohol Inhibits NR2B-Containing NMDA Receptors in the Ventral Bed Nucleus of the Stria Terminalis

Alcohol Inhibits NR2B-Containing NMDA Receptors in the Ventral Bed Nucleus of the Stria Terminalis

Synaptic Effects Induced by Alcohol

Presynaptic Ethanol Actions: Potential Roles in Ethanol Seeking

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