Inhibition by ethanol of excitatory amino acid receptors in rat locus coeruleus neurons in vitro

Nieber, K; Poelchen, Wolfgang; Sieler, D.; Illéš, Peter

doi:10.1007/pl00005171

Cited by 28 publications

(24 citation statements)

References 39 publications

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“…Ethanol inhibition of NMDA receptor activation in RVLM neurons was detected not only during systemic administration but also during bath superfusion in a single neuron in vitro. The concentrations used in our in vitro electrophysiological study were similar to the effective concentrations reported for various neurons in slice preparations [18,21,30,33]. It is interesting to note the differences in ethanol potency between the inhibitions of NMDA-induced pressor effects in vivo and the NMDA-mediated inward currents in vitro.…”

Section: Discussionmentioning

confidence: 49%

“…Since the initial report by Lovinger et al [20] on the ability of ethanol to inhibit NMDA-receptor-mediated currents in the mouse hippocampus, the effects of ethanol on NMDA receptor activation have been examined extensively in various neuronal preparations from CNS and cultured neurons. In rats, for example, acute exposure to ethanol in vitro inhibited NMDA-mediated responses in the nucleus accumbens [29], the hippocampus [21], the locus ceruleus [30], the cortical neurons [25], the spinal motor neurons [40] and the SPN [18]. In contrast, chronic ethanol treatment resulted in supersensitivity to NMDAmediated events, which are thought to be involved in the development of both ethanol tolerance and subsequent withdrawal hyperexcitability [8,36].…”

Section: Introductionmentioning

confidence: 99%

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Acute Tolerance to Ethanol Inhibition of NMDA-Induced Responses in RatRostral Ventrolateral Medulla Neurons

Lai¹,

Chang²,

Lin³

2004

J Biomed Sci

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The present study was performed to examine the effects of acute ethanol exposure on N-methyl-D-aspartate (NMDA)-induced responses and the development of acute tolerance in rat rostral ventrolateral medulla (RVLM) in vivo and in vitro. Repeated microinjections of NMDA (0.14 nmol) into the RVLM every 30 min caused reproducible increases in mean arterial pressure in urethane-anesthetized rats weighing 325–350 g. Intravenous injections of ethanol (0.16 or 0.32 g, 1 ml) inhibited NMDA-induced pressor effects in a blood-concentration-dependent and reversible manner. The inhibitory effect of ethanol was reduced over time during continuous infusion of ethanol or on the second injection 3.5 h after prior injection of a higher dose of ethanol (0.32 g). A high dose of ethanol (0.32 g) had no significant effects on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, γ-aminobutyric acid and glycine-induced changes in blood pressure. In vitro studies showed that ethanol (10– 100 mM) dose-dependently inhibited inward currents elicited by pressure ejection of NMDA (10 mM) in RVLM neurons of neonatal brainstem slice preparations. When the superfusion time of ethanol (100 mM) was increased to 50 min, its inhibitory effect decreased gradually after 30–40 min in 60% of RVLM neurons examined. These data suggested that ethanol inhibition and subsequent tolerance development is associated with changed sensitivity to NMDA in the RVLM, which may play important roles in the ethanol regulation of cardiovascular function.

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Section: Discussionmentioning

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Acute Tolerance to Ethanol Inhibition of NMDA-Induced Responses in RatRostral Ventrolateral Medulla Neurons

Lai¹,

Chang²,

Lin³

2004

J Biomed Sci

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“…EtOH also inhibits the function of AMPARs, and effects can be seen at concentrations as low as 10 mM (Akinshola 2001;Akinshola et al 2003;Dildy-Mayfield and Harris 1992;Möykkynen et al 2003;Nieber et al 1998;Wirkner et al 2000). In neurons from the brain, EtOH generally shows lower potency for inhibition of AMPARs in comparison to NMDARs (Frye and Fincher, 2000;Lovinger et al 1989;Lovinger 1995).…”

Section: Ligand-gated Ion Channels and Postsynaptic Ethanol Effectsmentioning

confidence: 99%

Synaptic Effects Induced by Alcohol

Lovinger

Roberto

2010

Current Topics in Behavioral Neurosciences

115

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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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“…For example, this method was recently used to demonstrate that, in locus coeruleus neurons recorded in pontine slices, ethanol significantly inhibits EPSPs while having no significant effects on IPSPs or membrane properties of these cells (Nieber et al, 1998). Evans and colleagues (2000) recently used intracellular recordings in inferior colliculus neurons to characterize hyperexcitability associated with ethanol withdrawal.…”

Section: Intracellular (Sharp) Electrode Recordingmentioning

confidence: 99%

Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

Valenzuela¹

2004

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SUPPLEMENTARY NOTES 12a. DISTRIBUTION /AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited 12b. DISTRIBUTION CODE Abstract (Maximum 200 Words) labstract should contain no proprietary or confidential information)We have been testing the hypothesis that chronic alcohol exposure alters expression and/or function of kainate receptors (KA-Rs) in the hippocampus. KA-Rs control hippocampal excitability and an ethanol-induced upregulation of KA-Rs could contribute to the hyperexcitability associated with alcohol withdrawal. Unexpectedly, Western immunoblotting and immunohistochemical studies have demonstrated that chronic ethanol exposure does not upregulate KA-R subunit expression. However, studies with cultured neurons suggest that alcohol withdrawal itself, but not chronic ethanol exposure, upregulates KA-R function. Therefore, we are now focusing our efforts at testing if this is also true for animals exposed to ethanol. We have switched to a different method of alcohol exposure; we are using the inhalation route, which reproducibly produces high ethanol levels. We are currently processing brain sections from control rats and rats withdrawn from a 14-day inhalational ethanol exposure paradigm. These sections will be immunostained with anti-GluR6/7 antibodies and will be used for radioligand binding experiments. We have also characterized the acute effects of ethanol on the function of interneuronal KA-Rs. Moreover, a preliminary experiment with hippocampal slices from rats withdrawn from a 6-day inhalational exposure paradigm suggests that the function of these receptors is upregulated. During the last year of support, we will concentrate on characterizing the function of KA-Rs in the CA1 and CAS regions in alcohol withdrawn rats. Alcohol-related medical disorders affect many organs and systems of the body, including the central nervous system (CNS). As with other drugs of abuse, long-term alcohol ingestion results in the development of tolerance, addiction, and dependence. Alcohol produces these effects by altering the actions of neurotransmitters and their receptors in the brain. Chronic ethanol exposure has complex and long-lasting effects on the function and/or expression of a myriad of neurotransmitter receptors and their modulators. A group of proteins affected by chronic ethanol exposure are hgand-gated ion channels such as the glutamatergic ionotropic receptors. Glutamate activates three major classes of ionotropic receptors. These three major types of channels are the NMD A, AMPA and kainate receptors (KA-Rs). The purpose of this proposal is to test whether or not chronic ethanol exposure results in alterations in subunit expression and/or function of KA-Rs in the hippocampus. Maladaptive changes in hippocampal KA-R expression could contribute to the pathophysiology of alcohol withdrawal syndrome. The alcohol withdrawal syndrome is associated with neuronal hyperexcitabiUty and seizures. Since kainate receptors are important regulators of excitability in the hippocampus, upregulation o...

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Inhibition by ethanol of excitatory amino acid receptors in rat locus coeruleus neurons in vitro

Cited by 28 publications

References 39 publications

Acute Tolerance to Ethanol Inhibition of NMDA-Induced Responses in RatRostral Ventrolateral Medulla Neurons

Acute Tolerance to Ethanol Inhibition of NMDA-Induced Responses in RatRostral Ventrolateral Medulla Neurons

Synaptic Effects Induced by Alcohol

Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

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