Ethanol inhibition of NMDA currents in acutely dissociated medial septum/diagonal band neurons from ethanol dependent rats

Grover, Cathy A.; Wallace, Kathleen; Lindberg, Scott A; Frye, Gerald D.

doi:10.1016/s0006-8993(97)01001-9

Cited by 27 publications

(45 citation statements)

References 70 publications

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“…Although several in vitro studies have demonstrated inhibition of NMDA-gated currents by ethanol (Lovinger, 1995;Grover et al, 1998;Ming et al, 2001), the brain sites investigated did not include the lateral septum to determine whether ethanol would be without effect at this site. In vitro studies of the effect of ethanol on GABA-gated currents have been equivocal.…”

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confidence: 99%

Comparison of Effect of Ethanol onN-Methyl-d-aspartate- and GABA-Gated Currents from Acutely Dissociated Neurons: Absence of Regional Differences in Sensitivity to Ethanol

Criswell¹,

Zhang²,

Griffith³

et al. 2003

J Pharmacol Exp Ther

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In vivo, ethanol alters the effect of N-methyl-D-aspartate (NMDA) and GABA in some brain regions but is without effect in others. To determine whether these regional differences were due to differences in the effect of ethanol on postsynaptic NMDA or GABA A receptors, we examined the effect of ethanol on NMDA-and GABA-gated currents from neurons acutely dissociated from the lateral septal nucleus, substantia nigra, thalamus, hippocampus, and cerebellum. Ethanol decreased the effect of NMDA similarly in all brain areas tested and had similar effects on Chinese hamster ovary cells expressing NR2A or NR2B subunits with an NR1-1a subunit. However, ifenprodil reduced the inhibition by ethanol of NMDA-gated currents from neurons isolated from the lateral septum without affecting neurons from the substantia nigra. In contrast to the robust effect of ethanol on NMDA-gated currents, ethanol (25-300 mM) was without effect on GABA-gated currents at all brain sites tested or on Ltk Ϫ cells stably expressing the ␣1, ␤2, and ␥2L or ␥2S subunits. The neuroactive steroid alphaxalone profoundly enhanced GABA-gated currents in all brain areas and cell types tested, indicating a similar sensitivity to allosteric modulation; however, there was no interaction of alphaxalone with ethanol at any site tested. These data suggest that the regional differences in the effect of ethanol observed in vivo are not due to a differential action of ethanol at the postsynaptic NMDA or GABA A receptor subtypes.

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mentioning

confidence: 99%

Comparison of Effect of Ethanol onN-Methyl-d-aspartate- and GABA-Gated Currents from Acutely Dissociated Neurons: Absence of Regional Differences in Sensitivity to Ethanol

Criswell¹,

Zhang²,

Griffith³

et al. 2003

J Pharmacol Exp Ther

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“…An increase in the component of current mediated by NR2B-containing receptors has also been observed (Floyd et al 2003;Kash et al 2009;Roberto et al 2004b. Interestingly, acute EtOH inhibition of NMDARs in most brain regions is still intact or even increased after chronic in vivo exposure (Floyd et al 2003;Roberto et al 2004b), although a small decrease in inhibition was observed in medial septum/diagonal band neurons (Grover et al 1998). Evidence of tolerance to EtOH inhibition during acute exposure has also been observed in hippocampal slices (Grover et al 1994;Miyakawa et al 1997).…”

Section: Chronic Ethanol Effects On Glutamatergic Transmission and Glmentioning

confidence: 80%

“…Chronic EtOH exposure generally produces an increase in the function of NMDARs and in NMDAR-mediated glutamatergic synaptic transmission (Cebere et al 1999;Grover et al 1998;Gulya et al 1991;Lack et al 2007;Smothers et al 1997) (Fig. 1d).…”

Section: Chronic Ethanol Effects On Glutamatergic Transmission and Glmentioning

confidence: 92%

“…Furthermore, changes in responses to NMDAR activation were consistently larger than changes in the effects of activation of other ionotropic glutamate receptors (Chandler et al 1997;Gulya et al 1991;Smothers et al 1997). Direct examination of ion current through the NMDAR pore has revealed effects consistent with a chronic EtOH-induced upregulation of NMDAR function (Floyd et al 2003;Grover et al 1998). An increase in the component of current mediated by NR2B-containing receptors has also been observed (Floyd et al 2003;Kash et al 2009;Roberto et al 2004b.…”

Section: Chronic Ethanol Effects On Glutamatergic Transmission and Glmentioning

confidence: 99%

“…1d). Initial studies examined effects of receptor activation on neuronal calcium and nitric oxide signals either in preparations made from EtOH-exposed animals or in cultured neurons treated with EtOH in the medium (Grover et al 1998;Gulya et al 1991;Chandler et al 1997;Iorio et al 1992;Smothers et al 1997). Exposure to EtOH for days to weeks increased NMDAR agonist-induced increases in intracellular calcium.…”

Section: Chronic Ethanol Effects On Glutamatergic Transmission and Glmentioning

confidence: 99%

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Synaptic Effects Induced by Alcohol

Lovinger

Roberto

2010

Current Topics in Behavioral Neurosciences

114

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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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