![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
NEUROPHARMACOLOGY
VA Eastern Colorado Health Care System, Medical Research Service, Denver, Colorado (P.H.W., W.R.P.); Department of Psychiatry, University of Colorado Health Sciences Center, Denver, Colorado (P.H.W., W.R.P.); and the Institut fur Neurophysiologie, Heinrich-Heine-Universitat, Dusseldorf, Germany (W.P.)
Received August 3, 2004; accepted December 17, 2004.
 |
Abstract |
|---|
 Top Abstract Materials and MethodsResultsDiscussionReferences |
|---|
, 
, and 
subunits and have selective cellular localization (Mohler et al., 2002
). In hippocampal CA1 neurons, the 1 subunit of GABAA 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 GABAA 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 and Mihic, 2004).
Studies to demonstrate ethanol potentiation of stimulus-evoked GABAA 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,b; Soldo et al., 1994; Lovinger, 1997; Weiner et al., 1997; Grobin et al., 1998; Mihic, 1999). Despite these disparate findings, the bulk of evidence indicates that ethanol can directly enhance the activity of postsynaptic GABAA receptor-mediated chloride channels (Faingold et al., 1998; Grobin et al., 1998; Harris and Mihic, 2004). Recent studies have shown that ethanol could enhance GABAA IPSCs via presynaptic interactions at GABAergic synapses (Weiner et al., 1997; Roberto et al., 2003; Ariwodola and Weiner, 2004).
Activation of GABAA receptors in the septohippocampal pathway has also been shown to potentiate behavioral effects of several anesthetics (Ma et al., 2002) as well as ethanol (Mihic et al., 1997). Electrophysiological studies have shown that GABAA IPSCs evoked in the CA1 hippocampal stratum pyramidale (proximal) subfield are enhanced to a greater extent by ethanol than GABAA IPSCs evoked in the stratum lacunosum-moleculare (distal) subfield (Weiner et al., 1997); however, the mechanisms that mediate the differential effect of ethanol on GABA currents evoked at these two pyramidal cell subfields are not well understood. The fact that zolpidem produced a similar enhancement of GABAA IPSCs at both proximally evoked (proximal GABAA IPSCs) and distally evoked (distal GABAA IPSCs) locations (Weiner et al., 1997) would seem to preclude the possibility that differences in GABAA receptor composition may underlie the differential ethanol sensitivity of GABAA IPSCs evoked at these two subfields in hippocampal CA1 pyramidal neurons. Other studies (Wan et al., 1996; Roberto et al., 2003; Ariwodola and Weiner, 2004) showed that a GABAB receptor antagonist can augment the ethanol enhancement of GABAA IPSCs, implying the involvement of GABAB receptors in modulating ethanol effects of GABAA responses in the hippocampus, but the mechanisms are not well understood.
GABAB receptors mediate the slow synaptic inhibitory response of GABA transmission (Solis and Nicoll, 1992) and are found in both the presynaptic and postsynaptic elements of GABAergic terminals. The GABAB receptor is a typical seven transmembrane G protein-coupled receptor and is known to exert its action through the interaction with Go/i and G subunits that modulate presynaptic calcium channels (Dittman and Regehr, 1996; Kubota et al., 2003) to regulate GABA release. The GABAB 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 GABAB receptor response (Frye and Fincher, 1996; Roberto et al., 2003), blockade of the GABAB receptor in CA1 neurons was shown to increase ethanol potentiation of the GABAA response (Wan et al., 1996).
In the current study, we test the hypothesis that differences in GABAB receptor function may underlie the differential ethanol sensitivity of GABAA IPSCs observed in proximal and distal locations of CA1 pyramidal neurons. The results of this study support this concept and implicate a significant modulatory role of postsynaptic GABAB receptor activity in the differential ethanol sensitivity between proximal and distal subfields in hippocampal CA1 pyramidal neurons.
|
Materials and Methods |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
), transverse hippocampal slices (400 µm) were prepared from 6- to 8-week-old male Sprague-Dawley rats with a Sorvall tissue chopper (Sorvall, Newtown, CT). Slices were made in ice-cold artificial cerebrospinal fluid (aCSF) and were stored in a submersion chamber at 32°C in aCSF containing 126 mM NaCl, 3 mM KCl, 1.5 mM MgCl2, 2.4 mM CaCl2, 1.2 mM NaH2PO4, 11 mM glucose, and 26 mM NaHCO3 saturated with 95% O2/5% CO2.
Electrophysiological Recordings and Drug Application. Hippocampal slices were transferred to a submersion recording chamber (H and H Custom Machining, Denver, CO) and superfused with gassed (95% O2/5% CO2) aCSF at a flow rate of 2 ml/min. Whole-cell patch-clamp recordings were made from CA1 pyramidal neurons at 32°C using an Axoclamp-2A amplifier (Axon Instruments Inc., Union City, CA) operating in voltage-clamp mode. Cells were not included in this study if their resting membrane potential was depolarized more than –65 mV (corrected for the liquid junction potential), if their access resistance was greater than 30 M
, or if this value changed by >15% over the course of the recording. Cells were voltage-clamped to approximately –55 mV to increase the chloride driving force to obtain GABAA IPSC responses of 50 to 100 pA (approximately 10–30% of the maximal response). Recording electrodes were constructed from fiber-containing borosilicate glass (1.5 mm o.d., 0.86 mm i.d.; Sutter Instrument Company, Navato, CA) and had resistances of 6 to 9 M when filled with the following internal K+-gluconate solution: 125 mM potassium gluconate, 1.5 mM KCl, 10 mM HEPES, 0.1 mM CaCl2, 1.0 mM EGTA, 2.0 mM Mg2+-ATP, and 0.2 mM GTP, pH adjusted to 7.25 with KOH, 290 ± 5 mOsM. This solution was kept on ice until immediately before use. All drugs used to make up the aCSF and internal recording solution were purchased from Sigma-Aldrich (St. Louis, MO). Ethanol and the receptor antagonists listed below were added to the artificial cerebrospinal fluid in known concentrations immediately before flowing into the slice chamber by direct infusion via calibrated syringe pumps (Razel Scientific Instruments, Stamford, CT). Glutamatergic N-methyl-D-aspartic acid (NMDA) and -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists DL(–)-2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt (CNQX) and the GABAA receptor antagonist bicuculline methiodide (BMI) were also purchased from Sigma-Aldrich. The GABAB receptor antagonist CGP-52432 was purchased from Tocris Cookson Inc. (Ellisville, MO). An 8.0 M ethanol solution (in deionized water) was prepared immediately before each experiment from a 95% stock solution (Aaper Alcohol and Chemical, Shelbyville, KT) and kept in a glass storage bottle at 4°C.
Proximal and Distal GABAA and GABAB Receptor-Mediated IPSCs. Evoked GABAA IPSCs were pharmacologically isolated by superfusion with the glutamatergic receptor antagonists APV (50 µM) and CNQX (20 µM) to block NMDA and AMPA receptors, respectively. Synaptic stimulation was delivered with the use of two bipolar twisted tungsten wire electrodes (0.2-ms pulses of 3–8 V), one placed in the stratum lacunosum-moleculare layer (for distal stimulation) and the other within 250 µm of the recorded cell soma in the CA1 stratum pyramidale (for proximal stimulation), as illustrated in Fig. 1A. An interstimulation interval of 20 s was used, and the stimulus intensities were adjusted to evoke proximal and distal IPSCs of similar amplitude. When GABAB responses were isolated by superfusion with the GABAA receptor antagonist BMI, the remaining GABAB component was completely blocked by CGP-52432. For determinations of the extent of the GABAB fraction in proximal and distal responses, the percentage of the total GABA IPSC remaining following BMI treatment was calculated. Paired-pulse depression in these CA1 pyramidal neurons was investigated by delivering the stimuli to the electrodes located at both the proximal and distal subfields of the neuron. The paired-pulse stimuli were determined at an interpulse interval of 30 or 50 ms. Both intervals gave similar results, so data from both conditions were combined for the data analysis. The amplitudes of the evoked responses were measured, and the paired-pulse index (PPI) was calculated as the ratio of the two responses (second/first). Curve fitting was determined from responses to single pulses obtained throughout each experiment.
|
In some experiments, differential interference contrast microscopy was used to measure the effect of ethanol from brief, local, direct pressure application of GABA to the soma or dendrites of CA1 pyramidal neurons. Micropipettes containing 10 mM GABA were placed 3 to 5 µm from the cell body or major dendritic process under visual control. GABA was delivered through the micropipette (5–10 ms at 10–20 psi) via a Picosprizer II (General Valve, Fairfield, NJ). Control responses were recorded, and then ethanol (80 mM) and/or CGP-52432 was applied by bath superfusion, and the GABA-evoked responses were measured before, during, and after washout of ethanol.
Statistical Analysis. Drug effects were quantified as the percentage of change in amplitude under the curve of the GABAA IPSCs following drug application relative to the mean control and washout values. Statistical analyses were carried out with the use of SigmaStat (SPSS Inc., Chicago, IL). The minimal significance level was set at p < 0.05.
|
Results |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
). Statistical analysis of the present data shows that there is a significant ethanol concentration versus hippocampal subfield interaction [F(4,74) = 3.447, p < 0.012, two-way ANOVA]. Thus, ethanol exhibited differential potentiation of GABAA IPSCs in the proximal and distal subfields of hippocampus over this ethanol concentration range tested (40–120 mM). Effect of GABAB Receptor Activity on Ethanol Potentiation of GABAA IPSCs. GABAA IPSC traces typically show that, under most recording conditions, the proximal GABA IPSC responses have a smaller late GABAB IPSC component than those evoked distally (Fig. 2, A1 and B1). Regardless of the proportion or size of the GABAB component, after pharmacological isolation with a GABAA antagonist, BMI (10 µM), ethanol (80 mM) treatment did not significantly modify these GABAB responses by either proximal (103 ± 9.8% of control, n = 7) or distal (102 ± 7.2% of control, n = 7) stimulation (Fig. 2, A2 and B2). Systematic subfield stimulation studies in the same CA1 pyramidal neurons in which GABA IPSCs were alternately evoked from proximal and distal locations show that the mean distally evoked GABA IPSC contains a significantly larger late GABAB IPSC component than the mean proximally evoked GABA IPSC (Fig. 2C) (Student's t test, t = 3.209, p < 0.006). Furthermore, a significant correlation is seen between the ethanol potentiation of GABAA IPSC and GABAB content; neurons having a smaller GABAB component have greater responses to ethanol [F(1,24) = 14.878, p < 0.001, linear regression analysis] (Fig. 2D).
|
To determine the effect of the possible GABAB receptor activity on the ethanol enhancement of the GABAA responses, we repeated the ethanol experiments in the presence of CGP-52432, a selective GABAB receptor antagonist, to block the GABAB IPSC component (Fig. 3, A1 and B1). Pretreatment of hippocampal slices with CGP-52432 shows that 80 mM ethanol now potentiates both the proximal and distal GABAA IPSCs (Fig. 3, A2 and B2, respectively), and the enhancement is reversed upon washout of ethanol; however, the CGP-52432 block of the GABAB component was not completely reversed after 30 min of washout (Fig. 3, A3 and B3). Composite results show that, in the presence of the GABAB antagonist, 80 mM ethanol potentiates GABAA IPSCs from the distally evoked location similarly to the ethanol enhancement via proximal stimulation (Fig. 3C) and that the proximal GABAA IPSCs were not further enhanced by the pretreatment of slices with CGP-52432.
|
Ethanol Enhancement of GABAA IPSCs: Presynaptic and/or Postsynaptic? A paired-pulse stimulation paradigm was used to examine a possible presynaptic role in the differential ethanol enhancement of proximal and distal GABAA IPSC responses. An increase in the second of two closely paired stimulations (30–50 ms apart) is thought to mainly be due to a presynaptic mechanism involving the phenomena of a higher probability of neurotransmitter vesicular release. Single and double (paired-pulse) GABAA IPSC responses were alternatively evoked in both proximal and distal locations on CA1 hippocampal pyramidal neurons (Fig. 4). The PPI was measured before and during ethanol (80 mM) treatment (Fig. 4, A1 and B1). The PPI was determined as the ratio of the second peak amplitude response (P2, above the decay phase of the first peak) divided by the peak amplitude of the first peak (P1) as shown in Fig. 4B1. Ethanol treatment resulted in a significant increase in the proximally stimulated PPI (Fig. 4A1) (control: 0.63 ± 0.039, n = 11; ethanol: 0.90 ± 0.085, n = 10, p = 0.005), but no significant effect was measured by distal stimulation (Fig. 4B1) (control: 0.64 ± 0.028, n = 13; ethanol: 0.75 ± 0.070, n = 10, p = 0.186). However, in the presence of the GABAB antagonist CGP-52432, ethanol at both proximally and distally evoked sites show increased PPI (proximal, Fig. 4A2: 0.86 ± 0.051, n = 11, p = 0.013; distal, Fig. 4B2: 0.87 ± 0.052, n = 12, p = 0.003). The composite data from all cells tested are shown in Fig. 4C. Interestingly, CGP-52432 treatment alone significantly increased the PPI at both proximal (0.85 ± 0.073, n = 11, p = 0.018) and distal (0.86 ± 0.064, n = 13, p = 0.004) stimulation sites.
|
Finally, local application of GABA directly onto the somatic or dendritic subfields of CA1 neurons was used to test for the effects of ethanol on postsynaptic GABA responses. Brief pressure application (10–20 psi, 5–15 ms) of GABA onto the proximal subfield produces a GABA response that is enhanced by ethanol in the presence or absence of the GABAB antagonist CGP-52432 (Fig. 5, A1 and A2). In contrast, although the application of GABA onto the dendritic subfield of CA1 neurons produces a robust GABA response, ethanol in the absence of the GABAB receptor antagonist does not significantly enhance the GABA response (Fig. 5B1). However, in the slices pretreated with CGP-52432, ethanol application produces a significant increase in the GABA response (Fig. 5B2). A comparison of the mean values during ethanol and/or CGP-52432 treatment (Fig. 5C) shows that, in the presence of CGP-52432, ethanol enhances responses to local GABA application to a similar extent in both proximal and distal subfields.
|
|
Discussion |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
; Mihic, 1999; Blednov et al., 2003), recent studies have shown that ethanol increased spontaneous GABA IPSC frequency in rat CA1 pyramidal neurons (Ariwodola and Weiner, 2004) and rat amygdala neurons (Roberto et al., 2003; Nie et al., 2004). These studies support the concept that ethanol may also increase the GABAA IPSC response via enhancement of presynaptic GABA release. Since pretreatment of hippocampal slices with a threshold concentration of 500 nM baclofen prevented ethanol (80 mM) from enhancing the proximally evoked GABAA IPSCs and can even cause IPSC inhibition by ethanol at a higher baclofen concentration (1.25 µM), Ariwodola and Weiner (2004) concluded that presynaptic GABAB receptors may modulate the actions of ethanol in the proximal subfield of CA1 pyramidal neurons in the hippocampus. On the other hand, our data show that proximally evoked GABAA IPSCs are enhanced to a similar extent by ethanol with or without pretreatment of a GABAB receptor antagonist, suggesting either very low endogenous GABAB receptor activity (our present results) or that ethanol enhancement of the proximal GABAA IPSC is not significantly modulated by presynaptic GABAB receptor activity. A low presynaptic GABAB activity at proximal GABAergic synapses would imply that inhibition of GABAB receptors would have little or no effect on the increase in probability of GABA release measured by paired-pulse stimulation. However, our experiments show that CGP-52432 enhances the paired-pulse ratio to a similar extent in both the proximally and distally evoked GABAA IPSCs, suggesting similar endogenous presynaptic GABAB receptor activity in both subfields of CA1 pyramidal neurons. Therefore, the differential sensitivity to ethanol in proximally and distally evoked GABAA IPSCs cannot be explained readily by differences in presynaptic GABAB receptor activity alone. In addition, presynaptic GABAB receptors have been shown to be inoperative under control or basal conditions in the adult CNS (Otis and Mody, 1992; McLean et al., 1996) unless tested under conditions causing large GABA release, such as during intense electrical stimulation (Deisz and Prince, 1989; Davies et al., 1993; Isaacson et al., 1993).
Evidence for a postsynaptic GABAB receptor-mediated IPSC has been shown in hippocampal neurons (Thalmann, 1988). This late inhibitory postsynaptic potential was mediated by pertussis toxin-sensitive, G protein-mediated activation of G protein-coupled inwardly rectifying potassium channels and inhibition of N-type Ca2+ channels (Bertrand et al., 2003). The activation of this postsynaptic GABAB IPSC was thought to enhance neuronal inhibition at GABAergic synapses (Pham et al., 1998). To circumvent the effect of presynaptic GABAB receptor regulation of GABA release at the GABAergic synapses, we pressure-applied 10 mM GABA locally onto proximal or distal subfields of CA1 pyramidal neurons. Under these experimental conditions, ethanol enhanced proximally evoked GABAA IPSCs similarly in the absence or presence of a GABAB receptor antagonist, suggesting a minimal role for GABAB regulation of ethanol effects on these proximal GABAA IPSCs. In contrast, ethanol alone did not enhance the distally evoked GABAA IPSCs, but it did enhance the distal GABAA IPSCs in the presence of a GABAB receptor antagonist. Thus, our data suggest that the differences in ethanol sensitivity at proximally and distally evoked GABAA IPSCs may be due to differences in the levels of postsynaptic GABAB receptor number and/or activity between these two CA1 subfields. Since ethanol alone failed to increase the probability of GABA release in the distal GABAergic synapses, we conclude that differences in both presynaptic and postsynaptic GABAB receptor activity may modulate the differential ethanol effects on GABAA IPSCs in these two subfields in CA1 pyramidal neurons. Future studies are designed to use receptor antagonists and manipulations that are selective to presynaptic or postsynaptic GABAB subtypes to elucidate the precise mechanisms of ethanol action in these hippocampal neurons.
|
Acknowledgements |
|---|
|
Footnotes |
|---|
ABBREVIATIONS: EtOH, ethanol; IPSC, inhibitory postsynaptic current; aCSF, artificial cerebrospinal fluid; NMDA, N-methyl-D-aspartic acid; AMPA, -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; APV, DL(–)-2-amino-5-phosphonovaleric acid; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt; BMI, bicuculline methiodide; CGP-52432, 3[[(3,4-dichlorophenyl)methyl]amino]propyl](diethoxymethyl) phosphinic acid; PPI, paired-pulse index; ANOVA, analysis of variance.
Address correspondence to: Dr. William R. Proctor, Dept. of Psychiatry (C-261), University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262. E-mail: bill.proctor{at}uchsc.edu
|
References |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Aguayo LG (1990) Ethanol potentiates the GABAA-activated Cl– current in mouse hippocampal and cortical neurons. Eur J Pharmacol 187: 127–130.[CrossRef][Medline]
Allan AM, Burnett D, and Harris RA (1991) Ethanol-induced changes in chloride flux are mediated by both GABA(A) and GABA(B) receptors. Alcoholism Clin Exp Res 15: 233–237.[CrossRef][Medline]
Ariwodola OJ and Weiner JL (2004) Ethanol potentiation of GABAergic synaptic transmission may be self-limiting: role of presynaptic GABA-B receptors. J Neurosci 24: 10679–10686.
Bertrand S, Nouel D, Morin F, Nagy F, and Lacaille JC (2003) Gabapentin actions on Kir3 currents and N-type Ca2+ channels via GABAB receptors in hippocampal pyramidal cells. Synapse 50: 95–109.[CrossRef][Medline]
Blednov YA, Jung S, Alva H, Wallace D, Rosahl T, Whiting PJ, and Harris RA (2003) Deletion of the a1 or b2 subunit of GABAA receptors reduces actions of alcohol and other drugs. J Pharmacol Exp Ther 304: 30–36.
Davies CH, Pozza MF, and Collingridge GL (1993) CGP 55845A: a potent antagonist of GABAB receptors in the CA1 region of rat hippocampus. Neuropharmacology 32: 1071–1073.[CrossRef][Medline]
Deisz RA and Prince DA (1989) Frequency-dependent depression of inhibition in guinea-pig neocortex in vitro by GABAB receptor feed-back on GABA release. J Physiol (Lond) 412: 513–541.
Dittman JS and Regehr WG (1996) Contributions of calcium-dependent and calcium-independent mechanisms to presynaptic inhibition at a cerebellar synapse. J Neurosci 16: 1623–1633.
Faingold CL, N'Gouemo P, and Riaz A (1998) Ethanol and neurotransmitter interactions–from molecular to integrative effects. Prog Neurobiol 55: 509–535.[CrossRef][Medline]
Fritschy JM, Weinmann O, Wenzel A, and Benke D (1998) Synapse-specific localization of NMDA and GABAA receptor subunits revealed by antigen-retrieval immunohistochemistry. J Comp Neurol 390: 194–210.[CrossRef][Medline]
Frye GD and Fincher A (1996) Sensitivity of postsynaptic GABAB receptors on hippocampal CA1 and CA3 pyramidal neurons to ethanol. Brain Res 735: 239–248.[CrossRef][Medline]
Gahwiler BH and Brown DA (1985) GABAB-receptor-activated K+ current in voltage-clamped CA3 pyramidal cells in hippocampal cultures. Proc Natl Acad Sci USA 82: 1558–1562.
Grobin AC, Matthews DB, Devaud LL, and Morrow AL (1998) The role of GABA(A) receptors in the acute and chronic effects of ethanol. Psychopharmacology 139: 2–19.[CrossRef][Medline]
Harris RA (1999) Ethanol actions on multiple ion channels: which are important? Alcoholism Clin Exp Res 23: 1563–1570.[CrossRef][Medline]
Harris RA and Mihic SJ (2004) Alcohol and inhibitory receptors: unexpected specificity from a nonspecific drug. Proc Natl Acad Sci USA 101: 2–3.
Isaacson JS, Solis JM, and Nicoll RA (1993) Local and diffuse synaptic actions of GABA in the hippocampus. Neuron 10: 165–175.[CrossRef][Medline]
Kubota H, Katsurabayashi S, Moorhouse AJ, Murakami N, Koga H, and Akaike N (2003) GABAB receptor transduction mechanisms and cross-talk between protein kinases A and C, in GABAergic terminals synapsing onto neurons of the rat nucleus basalis of Meynert. J Physiol (Lond) 551: 263–276.
Lovinger DM (1997) Alcohols and neurotransmitter gated ion channels: past, present and future. Naunyn-Schmiedeberg's Arch Pharmacol 356: 267–282.[CrossRef][Medline]
Ma J, Shen B, Stewart LS, Herrick IA, and Leung LS (2002) The septohippocampal system participates in general anesthesia. J Neurosci 22: RC200.
McLean HA, Caillard O, Khazipov R, Ben-Ari Y, and Gaiarsa JL (1996) Spontaneous release of GABA activates GABAB receptors and controls network activity in the neonatal rat hippocampus. J Neurophysiol 76: 1036–1046.
Mihic SJ (1999) Acute effects of ethanol on GABAA and glycine receptor function. Neurochem Int 35: 115–123.[CrossRef][Medline]
Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MA, Finn SE, Mascia MP, Valenzuela CF, Hanson KK, Greenblatt EP, et al. (1997) Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors. Nature (Lond) 389: 385–389.[CrossRef][Medline]
Mohler H, Fritschy JM, and Rudolph U (2002) A new benzodiazepine pharmacology. J Pharmacol Exp Ther 300: 2–8.
Newberry NR and Nicoll RA (1984) Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. Nature (Lond) 308: 450–452.[CrossRef][Medline]
Nie ZG, Schweitzer P, Roberts AJ, Madamba SG, Moore SD, and Siggins GR (2004) Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Science (Wash DC) 303: 1512–1514.
Osmanovic SS and Shefner SA (1988) Baclofen increases the potassium conductance of rat locus coeruleus neurons recorded in brain slices. Brain Res 438: 124–136.[CrossRef][Medline]
Otis TS and Mody I (1992) Differential activation of GABAA and GABAB receptors by spontaneously released transmitter. J Neurophysiol 67: 227–235.
Pham TM, Nurse S, and Lacaille JC (1998) Distinct GABAB actions via synaptic and extrasynaptic receptors in rat hippocampus in vitro. J Neurophysiol 80: 297–308.
Poelchen W, Proctor WR, and Dunwiddie TV (2000) The in vitro ethanol sensitivity of hippocampal synaptic gamma-aminobutyric acidA responses differs in lines of mice and rats genetically selected for behavioral sensitivity or insensitivity to ethanol. J Pharmacol Exp Ther 295: 741–746.
Proctor WR, Allan AM, and Dunwiddie TV (1992a) Brain region-dependent sensitivity of GABAA receptor-mediated responses to modulation by ethanol. Alcoholism Clin Exp Res 16: 480–489.[CrossRef][Medline]
Proctor WR, Soldo BL, Allan AM, and Dunwiddie TV (1992b) Ethanol enhances synaptically evoked GABAA receptor-mediated responses in cerebral cortical neurons in rat brain slices. Brain Res 595: 220–227.[CrossRef][Medline]
Reynolds JN and Prasad A (1991) Ethanol enhances GABAA receptor-activated chloride currents in chick cerebral cortical neurons. Brain Res 564: 138–142.[CrossRef][Medline]
Roberto M, Madamba SG, Moore SD, Tallent MK, and Siggins GR (2003) Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons. Proc Natl Acad Sci USA 100: 2053–2058.
Siggins GR, Pittman QJ, and French ED (1987) Effects of ethanol on CA1 and CA3 pyramidal cells in the hippocampal slice preparation: an intracellular study. Brain Res 414: 22–34.[CrossRef][Medline]
Soldo BL, Proctor WR, and Dunwiddie TV (1994) Ethanol differentially modulates GABA-A receptor-mediated chloride currents in hippocampal, cortical and septal neurons in rat brain slices. Synapse 18: 94–103.[CrossRef][Medline]
Solis JM and Nicoll RA (1992) Pharmacological characterization of GABAB-mediated responses in the CA1 region of the rat hippocampal slice. J Neurosci 12: 3466–3472.[Abstract]
Somogyi P, Takagi H, Richards JG, and Mohler H (1989) Subcellular localization of benzodiazepine/GABAA receptors in the cerebellum of rat, cat and monkey using monoclonal antibodies. J Neurosci 9: 2197–2209.[Abstract]
Thalmann RH (1988) Evidence that guanosine triphosphate (GTP)-binding proteins control a synaptic response in brain: effect of pertussis toxin and GTP gamma S on the late inhibitory postsynaptic potential of hippocampal CA3 neurons. J Neurosci 8: 4589–4602.[Abstract]
Wan FJ, Berton F, Madamba SG, Francesconi W, and Siggins GR (1996) Low ethanol concentrations enhance GABAergic inhibitory postsynaptic potentials in hippocampal pyramidal neurons only after block of GABAB. Proc Natl Acad Sci USA 93: 5049–5054.
Weiner JL, Gu C, and Dunwiddie TV (1997) Differential ethanol sensitivity of subpopulations of GABAA synapses onto rat hippocampal CA1 pyramidal neurons. J Neurophysiol 77: 1306–1312.
This article has been cited by other articles:
|
|
 |
|
  J. H. Krystal, J. Staley, G. Mason, I. L. Petrakis, J. Kaufman, R. A. Harris, J. Gelernter, and J. Lappalainen {gamma}-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment. Arch Gen Psychiatry, September 1, 2006; 63(9): 957 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. R. Proctor, L. Diao, R. K. Freund, M. D. Browning, and P. H. Wu Synaptic GABAergic and glutamatergic mechanisms underlying alcohol sensitivity in mouse hippocampal neurons J. Physiol., August 15, 2006; 575(1): 145 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. DuBois, A. Perlegas, D. W. Floyd, J. L. Weiner, and B. A. McCool Distinct Functional Characteristics of the Lateral/Basolateral Amygdala GABAergic System in C57BL/6J and DBA/2J Mice J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 629 - 640. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|
 |
 |
 |
