Sensitivity of postsynaptic GABAB receptors on hippocampal CA1 and CA3 pyramidal neurons to ethanol

Frye, Gerald D.; Fincher, Annette S.

doi:10.1016/0006-8993(96)00579-3

Cited by 27 publications

(18 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, our data and those of others (Frye and Fincher, 1996;Wan et al, 1996) also suggest that ethanol does not enhance postsynaptic GABA B receptor function in the CA1 region. All GABA B receptors are heterodimers comprising GABA B1 and GABA B2 subunits (Bowery and Enna, 2000;Enna, 2001), and genetic deletion of the GABA B1 isoform completely abolishes presynaptic and postsynaptic GABA B receptor function (Prosser et al, 2001).…”

Section: Discussionsupporting

confidence: 64%

“…Ethanol pretreatment (80 mM) had no effect on currents evoked by 20 M baclofen (68.9 Ϯ 8.6 pA; n ϭ 5; p Ͼ 0.05). Although ethanol alone appeared to induce a small outward current in the example illustrated, this effect was not significant and has not been consistently observed in other studies (Frye and Fincher, 1996;Wan et al, 1996). …”

Section: Ethanol Increases Presynaptic Gaba B Receptor Activitycontrasting

confidence: 48%

“…Although this specific interaction has not been previously examined, several studies have characterized the acute effects of ethanol on postsynaptic GABA B receptor activity in the hippocampus and have reported no effect of ethanol at concentrations similar to those used in our studies (Frye et al, 1991;Frye and Fincher, 1996;Wan et al, 1996). We performed two separate experiments to evaluate possible effects of ethanol on postsynaptic GABA B receptor function under our recording conditions.…”

Section: Ethanol Increases Presynaptic Gaba B Receptor Activitymentioning

confidence: 89%

See 2 more Smart Citations

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABA_BReceptors

Ariwodola

Weiner²

2004

J. Neurosci.

138

137

View full text Add to dashboard Cite

Ethanol enhances GABAergic synaptic inhibition, and this interaction contributes to many of the behavioral and cognitive effects of this drug. Most studies suggest that ethanol enhances GABAergic neurotransmission via an allosteric potentiation of the postsynaptic GABA A receptors that mediate fast synaptic inhibition in the mammalian CNS. Despite widespread acceptance of this hypothesis, direct support for such a mechanism has been difficult to obtain. Ethanol does not enhance GABA A receptor function in all brain regions or under all experimental conditions, and factors responsible for this variability remain mostly unknown. Notably, blockade of GABA B receptors dramatically enhances ethanol potentiation of hippocampal GABA A IPSPs and IPSCs, suggesting that some unknown GABA B receptor mechanism limits the overall potentiating effect of ethanol on GABAergic synapses. In this study, we demonstrate that, at perisomatic synapses in the rat hippocampus, ethanol enhances presynaptic GABA B autoreceptor function and that this interaction reduces the overall potentiating effect of ethanol at these synapses. We further show that ethanol significantly elevates basal presynaptic GABA B receptor tone, possibly via an increase in spontaneous GABA release, and that pretreatment with a subthreshold concentration of the GABA B receptor agonist baclofen blocks ethanol but not flunitrazepam or pentobarbital potentiation of GABA A IPSCs. These data suggest that an interaction between ethanol and presynaptic GABA B autoreceptor activity regulates the ethanol sensitivity of GABAergic synapses. Given that the in vitro ethanol sensitivity of these synapses correlates with in vivo ethanol responsiveness in a number of rodent lines, our data further suggest that presynaptic GABA B receptor activity may play a role in regulating behavioral sensitivity to ethanol.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Ethanol Increases Presynaptic Gaba B Receptor Activitycontrasting

confidence: 48%

Section: Ethanol Increases Presynaptic Gaba B Receptor Activitymentioning

confidence: 89%

See 1 more Smart Citation

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABA_BReceptors

Ariwodola

Weiner²

2004

J. Neurosci.

138

137

View full text Add to dashboard Cite

show abstract

“…The GABA B receptor has also been shown to modify postsynaptic potassium conductance (Newberry and Nicoll, 1984;Gahwiler and Brown, 1985;Osmanovic and Shefner, 1988), thereby altering cell activity. Although ethanol had little direct effect on the GABA B receptor response (Frye and Fincher, 1996;Roberto et al, 2003), blockade of the GABA B receptor in CA1 neurons was shown to increase ethanol potentiation of the GABA A response (Wan et al, 1996).…”

mentioning

confidence: 91%

Differential GABA_B Receptor Modulation of Ethanol Effects on GABA_A Synaptic Activity in Hippocampal CA1 Neurons

Poelchen²,

Proctor³

2004

J Pharmacol Exp Ther

View full text Add to dashboard Cite

We tested the hypothesis that differential sensitivity to ethanol of synaptic GABA A somatic and dendritic inhibitory postsynaptic currents (IPSCs) in hippocampal CA1 pyramidal neurons could be due to differences in the extent of GABA B receptor activity at GABAergic synapses in these two hippocampal subfields. Our present results show that dendritic (distally evoked) GABA IPSCs contain a larger GABA B IPSC component of the total GABA IPSC than the somatic (proximally evoked) subfield. The inhibition of GABA B receptors by pretreatment of hippocampal slices with CGP-52432 [3[[(3,4-, a selective GABA B receptor antagonist, changes the basal ethanol-insensitive, distally evoked GABA A IPSCs to become more sensitive to ethanol. In addition, paired-pulse stimulation of the proximal and distal subfields of hippocampal pyramidal neurons shows that ethanol alone increases the probability of GABA release at proximal but not distal regions. Changes by ethanol on the probability of GABA release are only seen at distal locations during GABA B blockade. Finally, when the modulation of presynaptic GABA B receptors is minimized by the local application of 10 mM GABA directly onto somatic or dendritic GABAergic synaptic regions, postsynaptic GABA B receptors seem to exert significant negative (inhibiting) influence on the effects of ethanol on GABA A IPSCs in the distal subfields of CA1 pyramidal neurons. Together, our data suggest that differences in both presynaptic and postsynaptic GABA B receptor activity at these GABAergic synapses may modulate the differential ethanol sensitivity of proximal and distal GABA A IPSCs in hippocampal CA1 pyramidal neurons.GABA is a major inhibitory neurotransmitter in the brain and generates both fast and slow inhibitory synaptic activity in many types of neurons. There are two major types of GABA receptors (GABA A and GABA B ) that mediate GABA neurotransmission. The GABA A receptor is a ligand-gated chloride channel consisting of mainly pentameric subunit proteins that form the chloride ion channel pore. In the brain, the GABA A receptors consist of ␣, ␤, and ␥ subunits and have selective cellular localization (Mohler et al., 2002). In hippocampal CA1 neurons, the ␣ 1 subunit of GABA A receptors is distributed primarily on the dendritic region of the cell (Somogyi et al., 1989), whereas receptors with ␣ 2 subunits are more dense in the somal region (Fritschy et al., 1998). The particular type of subunits that compose a GABA A receptor determines the channel kinetics, affinity for GABA, rate of desensitization, and the modification of the channel activity by other pharmacological agents, including benzodiazepines, barbiturates, anesthetics, and most likely ethanol (Mohler et al., 2002: Harris andMihic, 2004).Studies to demonstrate ethanol potentiation of stimulusevoked GABA A inhibitory postsynaptic currents (IPSCs) at GABAergic synapses, however, have yielded conflicting results (Siggins et al., 1987;Aguayo, 1990;Allan et al., 1991;Reynolds and Prasad, 1991; Proctor et al., 1992a,...

show abstract

“…Chronic EtOH treatment (12 days) did not shift sensitivity or maximum response to baclofen in CA1 neurons. These results suggest that GABA B receptors in this model were essentially insensitive to EtOH (Frye and Fincher 1996). Melis et al (2002) linked the long-lasting potentiation of GABAergic synapses on dopaminergic neurons in the VTA by systemic EtOH to an effect on presynaptic GABA B receptors.…”

Section: γ-Aminobutyric Acid B Receptors and Chronic Ethanol Actionsmentioning

confidence: 60%

Synaptic Effects Induced by Alcohol

Lovinger

Roberto

2010

Current Topics in Behavioral Neurosciences

114

View full text Add to dashboard Cite

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.

show abstract

Sensitivity of postsynaptic GABAB receptors on hippocampal CA1 and CA3 pyramidal neurons to ethanol

Cited by 27 publications

References 41 publications

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABA_BReceptors

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABA_BReceptors

Differential GABA_B Receptor Modulation of Ethanol Effects on GABA_A Synaptic Activity in Hippocampal CA1 Neurons

Synaptic Effects Induced by Alcohol

Contact Info

Product

Resources

About

Sensitivity of postsynaptic GABAB receptors on hippocampal CA1 and CA3 pyramidal neurons to ethanol

Cited by 27 publications

References 41 publications

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABABReceptors

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABABReceptors

Differential GABAB Receptor Modulation of Ethanol Effects on GABAA Synaptic Activity in Hippocampal CA1 Neurons

Synaptic Effects Induced by Alcohol

Contact Info

Product

Resources

About

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABA_BReceptors

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABA_BReceptors

Differential GABA_B Receptor Modulation of Ethanol Effects on GABA_A Synaptic Activity in Hippocampal CA1 Neurons