Acute and Chronic Ethanol Alter Glutamatergic Transmission in Rat Central Amygdala: an<i>In Vitro</i>and<i>In Vivo</i>Analysis

Roberto, Marisa; Schweitzer, Paul; Madamba, Samuel G.; Stouffer, David G.; Parsons, Loren H.; Siggins, George R.

doi:10.1523/jneurosci.5077-03.2004

Cited by 286 publications

(401 citation statements)

References 68 publications

(77 reference statements)

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“…As previously observed in the hippocampus (Weiner et al, 1999), acute ethanol inhibited synaptically evoked postsynaptic amygdalar KA EPSCs more potently than either AMPA EPSCs, which were not affected by even the highest concentration of ethanol tested (80 mM), or NMDA receptor-mediated synaptic responses, which were only significantly inhibited at this highest concentration. These findings agree with other reports of postsynaptic inhibition of NMDA receptors by acute ethanol in isolated cells of the BLA (Floyd et al, 2003), in the hippocampus (Lovinger et al, 1989), central nucleus of the amygdala (Roberto et al, 2004) and the ventral bed nucleus of the stria terminalis (Kash et al, 2007). Acute ethanol has been shown to have no effect on AMPA receptors in the hippocampus with a small, 12% inhibition on composite AMPA and KA-R currents in cerebellar granular cells (Valenzuela et al, 1998).…”

Section: Acute Ethanol Inhibits Ka Epscs Via a Postsynaptic Mechanismsupporting

confidence: 92%

Ethanol inhibition of kainate receptor-mediated excitatory neurotransmission in the rat basolateral nucleus of the amygdala

et al. 2008

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The neurobiological mechanisms governing alcohol-induced alterations in anxiety-like behaviors are not fully understood. Given that the amygdala is a major emotional center in the brain and regulates the expression of both learned-fear and anxiety, neurotransmitter systems within the basolateral amygdala represent likely mechanisms governing the anxiety-related effects of acute ethanol exposure. It is well established that, within the glutamatergic system, N-methyl-D-aspartate (NMDA)-type receptors, are particularly sensitive to intoxicating concentrations of ethanol. However, recent evidence suggests that kainate-type glutamate receptors are sensitive to ethanol as well. Therefore, we examined the effect of acute ethanol on kainate receptor (KA-R)-mediated synaptic transmission in the basolateral amygdala (BLA) of Sprague Dawley rats. Acute ethanol decreased KA-R-mediated excitatory postsynaptic currents (EPSCs) in the BLA in a concentrationdependent manner. Ethanol also inhibited currents evoked by focal application of the kainate receptor agonist (R, S)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), and ethanol inhibition of kainate EPSCs was not associated with a change in paired-pulse ratio, suggesting a postsynaptic mechanism of ethanol action. The neurophysiological consequences of this acute sensitivity were tested by measuring ethanol's effects on KA-R-dependent modulation of synaptic plasticity. Acute ethanol, like the GluR5-specific antagonist (RS)-3-(2-carboxybenzyl)willardiine (UBP 296), robustly diminished ATPA-induced increases in synaptic efficacy. Lastly, to better understand the relationship between KA-R activity and anxiety-like behavior, we bilaterally microinjected ATPA directly into the BLA. We observed an increase in measures of anxiety-like behavior, assessed in the light/dark box, with no change in locomotor activity. This evidence suggests that kainate receptors in the BLA are inhibited by pharmacologically relevant concentrations of ethanol and may contribute to some of the acute anxiolytic effects of this drug.

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Section: Acute Ethanol Inhibits Ka Epscs Via a Postsynaptic Mechanismsupporting

confidence: 92%

Ethanol inhibition of kainate receptor-mediated excitatory neurotransmission in the rat basolateral nucleus of the amygdala

et al. 2008

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“…We found that 100 mM ethanol inhibited NMDA-EPSCs in vBNST neurons in the NR2A KO (6674% of baseline peak amplitude, n ¼ 5, po0.01, Figure 4a) to the same degree as in wild-type animals (Figure 4f), demonstrating that the presence of the NR2A subunit is not required for ethanol inhibition of NMDA-EPSCs in the vBNST. At some synapses, it has been suggested that NR2B-containing NMDARs are specifically targeted by ethanol (Roberto et al, 2004;Izumi et al, 2005). We utilized a pharmacological approach to test the role of NR2B subunits in ethanol sensitivity of the NMDA-EPSC.…”

Section: Nr2a Is Not Required For Ethanol Inhibition Of Nmda-epscs Inmentioning

confidence: 99%

“…Little is known, however, about the effects that acute ethanol administration has on neuronal function in this region. The N-methyl-D-asparate receptor (NMDAR) has been heavily implicated in the acute actions of ethanol in both behavioral (Boyce-Rustay and Holmes, 2005) and molecular studies (Roberto et al, 2004). NMDARs in the BNST have been specifically implicated in the regulation of stress and anxiety Pawlak et al, 2005), which have been suggested to be important in regulating ethanol-seeking behavior in humans and in animal models of alcohol drinking.…”

Section: Introductionmentioning

confidence: 99%

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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“…One mechanism for the change of NMDA receptor sensitivity has been proposed to involve alterations of NMDA receptor subunits (Sheela Rani and Ticku, 2006), since relatively little change of NMDA receptor density was observed after chronic ethanol treatment (Tremwel et al, 1994;Rudolph et al, 1997;Freund and Anderson, 1999). It has been observed that chronic ethanol treatment facilitated NMDA receptor function in the amygdala (Floyd et al, 2003;Roberto et al, 2004). Thus, the tolerance of LAMG neuronal firing to the first dose of binge ethanol observed in the present study may be related to adaptive changes of NMDA receptors induced by CIE administration.…”

Section: Discussionmentioning

confidence: 99%

“…The experience of repeated withdrawals from chronic ethanol treatment lead to a kindling-like process (Gonzalez et al, 2001), and chronic ethanol treatment potentiates seizures evoked by several convulsants (Kokka et al, 1993;Becker et al, 1998). It has been shown that chronic ethanol administration leads to facilitated NMDA receptor function (Floyd et al, 2003;Roberto et al, 2004) and altered GABA A receptor pharmacology and subunit expression (Floyd et al, 2004) in the amygdala. These data suggest that amygdala neurons may have different responses to chronic ethanol than those resulting from subacute ethanol administration.…”

Section: Introductionmentioning

confidence: 99%

The effects of chronic ethanol administration on amygdala neuronal firing and ethanol withdrawal seizures

Feng

Faingold

2008

Neuropharmacology

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SummaryPhysical dependence on ethanol results in an ethanol withdrawal (ETX) syndrome including susceptibility to audiogenic seizures (AGS) in rodents after abrupt cessation of ethanol. Chronic ethanol administration and ETX induce functional changes of neurons in several brain regions, including the amygdala. Amygdala neurons are requisite elements of the neuronal network subserving AGS propagation during ETX induced by a subacute "binge" ethanol administration protocol. However, the effects of chronic ethanol administration on amygdala neuronal firing and ETX seizure behaviors are unknown. In the present study ethanol (5 g/kg) was administered intragastrically in Sprague-Dawley rats once daily for 28 days [chronic intermittent ethanol (CIE) protocol]. One week later the rats began receiving ethanol intragastrically 3 times daily for 4 days (binge protocol). Microwire electrodes were implanted prior to CIE or on the day after CIE ended day 29 to record extracellular action potentials in lateral amygdala (LAMG) neurons. The first dose of ethanol administered in the binge protocol following CIE treatment did not alter LAMG neuronal firing, which contrasts with firing suppression seen previously in the binge protocol alone. These data indicate that CIE induces neuroadaptive changes in the ETX network which reduce LAMG response to ethanol. LAMG neuronal responses to acoustic stimuli prior to AGS were significantly decreased during ETX as compared to those before ethanol treatment. LAMG neurons fired tonically throughout the tonic convulsions during AGS. CIE plus binge treatment resulted in a significantly greater mean seizure duration and a significantly elevated incidence of death than was seen previously with the binge protocol alone, indicating an elevated seizure severity following chronic ethanol administration.

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Acute and Chronic Ethanol Alter Glutamatergic Transmission in Rat Central Amygdala: anIn VitroandIn VivoAnalysis

Cited by 286 publications

References 68 publications

Ethanol inhibition of kainate receptor-mediated excitatory neurotransmission in the rat basolateral nucleus of the amygdala

Ethanol inhibition of kainate receptor-mediated excitatory neurotransmission in the rat basolateral nucleus of the amygdala

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

The effects of chronic ethanol administration on amygdala neuronal firing and ethanol withdrawal seizures

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