Site-specific microinjection of Gaboxadol into the infralimbic cortex modulates ethanol intake in male C57BL/6J mice
Open accessAbstract
Extrasynaptic GABAA receptors, often identified as those containing both α4 and δ subunits, demonstrate super-sensitivity to GABA and are involved in tonic inhibitory processes regulating activity within mesolimbocortical circuitry. Rodent studies testing the effects of the δ-subunit selective agonist Gaboxadol (THIP) on alcohol consumption have produced mixed results. The goal of this study was to determine the role of extrasynaptic GABAA receptors located in the infralimbic cortex (ILC) in the alcohol consumption of male C57BL/6J (B6) mice. The ILC is of interest due to its demonstrated involvement in stress reactivity. Furthermore, alcohol exposure has been shown to interfere with extinction learning; impairments of which may be related to inflexible behavior (i.e., problematic alcohol consumption). Adult male B6 mice were bilaterally implanted with guide cannulas aimed at the ILC and were subsequently offered daily limited access to 20% ethanol or 5% sucrose for 7 days. Immediately prior to ethanol or sucrose access on day 7, mice were bilaterally injected with 50 or 100ng THIP (25 or 50ng per side respectively) or saline vehicle into the ILC. The highest dose of intra-ILC THIP (100ng/mouse) increased alcohol intake relative to vehicle controls, although control animals consumed relatively little ethanol following infusion. Intra-ILC THIP had no effect on sucrose consumption (p>0.05), suggesting that the effect of THIP was selective for ethanol consumption. Together, these findings suggest that THIP may have effectively prevented the decrease in ethanol intake on day 7 induced by the microinjection process, perhaps supporting a suggested role for the ILC in adaptive learning processes and behavioral flexibility.
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Ethanol consumption can be increased in a limited access paradigm when the activity of α4GABAARs in the mPFC is potentiated through gaboxadol.
“Similarly, ethanol consumption could be increased in a limited access paradigm when the activity of α4GABAARs in the mPFC was potentiated through gaboxadol [113].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [113]
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Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859 · see citing works
Koob, G. F., & Volkow, N. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.110 · Cited by 5,340 · see citing works
mouse brain in stereotaxic coordinates
Franklin, K. B. J., & Paxinos, G. (1997) · Cited by 3,258 · see citing works
Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors
Farrant, M., & Nusser, Z. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1625 · Cited by 2,081 · see citing works
Neurons in medial prefrontal cortex signal memory for fear extinction
Milad, M. R., & Quirk, G. J. (2002) · Nature · doi:10.1038/nature01138 · Cited by 1,836 · cited 1× · see citing works
“A role for the ILC in extinction learning (Milad and Quirk, 2002), behavioral flexibility (Kroener et al., 2012), and drug seeking (Peters et al., 2008a) has been demonstrated and chronic intermittent ethanol exposure can produce neurophysiological abnormalities in the ILC associated with these…”
Sesack, S. R., Deutch, A. Y., Roth, R. H., & Bunney, B. S. (1989) · Journal of Comparative Neurology · doi:10.1002/cne.902900205 · Cited by 1,568 · see citing works
Differential projections of the infralimbic and prelimbic cortex in the rat
Vertes, R. P. (2004) · Synapse · doi:10.1002/syn.10279 · Cited by 1,550 · see citing works
Fritschy, J., & Mohler, H. (1995) · Journal of Comparative Neurology · doi:10.1002/cne.903590111 · Cited by 1,244 · see citing works
Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors
Mihic, S. J., Ye, Q., Wick, M. J., Koltchine, V. V., Krasowski, M. D., Finn, S. E., Mascia, M. P., Valenzuela, C. F., Hanson, K. K., Greenblatt, E. P., et al. (1997) · Nature · doi:10.1038/38738 · Cited by 1,219 · see citing works
Quirk, G. J., Likhtik, E., Pelletier, J. G., & Paré, D. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-25-08800.2003 · Cited by 927 · see citing works
The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior
McFarland, K., & Kalivas, P. W. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-21-08655.2001 · Cited by 905 · see citing works
McFarland, K., Lapish, C. C., & Kalivas, P. W. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03531.2003 · Cited by 884 · see citing works
Petrides, M., & Pandya, D. N. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2001.02090.x · Cited by 882 · see citing works
Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice
Rhodes, J. S., Best, K., Belknap, J. K., Finn, D. A., & Crabbe, J. C. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.10.007 · Cited by 820 · see citing works
Pharmacological characterization of a novel cell line expressing human α4β3δ GABAA receptors
Brown, N. A., Kerby, J., Bonnert, T. P., Whiting, P. J., & Wafford, K. A. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704795 · Cited by 603 · see citing works
Gr�sser, S. M., Wrase, J., Klein, S., Hermann, D., Smolka, M. N., Ruf, M., Weber-Fahr, W., Flor, H., Mann, K., Braus, D. F., et al. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1828-4 · Cited by 598 · see citing works
Infralimbic Prefrontal Cortex Is Responsible for Inhibiting Cocaine Seeking in Extinguished Rats
Peters, J., LaLumiere, R. T., & Kalivas, P. W. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1045-08.2008 · Cited by 537 · see citing works
Chudasama, Y., Passetti, F., Rhodes, S. E. V., Lopian, D., Desai, A., & Robbins, T. W. (2003) · Behavioural Brain Research · doi:10.1016/j.bbr.2003.09.020 · Cited by 518 · see citing works
Wallner, M., Hanchar, H. J., & Olsen, R. W. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2435171100 · Cited by 463 · see citing works
Izquierdo, A., Wellman, C. L., & Holmes, A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0474-06.2006 · Cited by 459 · see citing works
Maldonado-Irizarry, C. S., Swanson, C., & Kelley, A. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-10-06779.1995 · Cited by 390 · see citing works
George, M. S., Anton, R. F., Bloomer, C., Tenebäck, C. C., Drobes, D. J., Lorberbaum, J. P., Nahas, Z. H., & Vincent, D. J. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.4.345 · Cited by 382 · see citing works
Mouse inbred strain differences in ethanol drinking to intoxication
Rhodes, J. S., Ford, M. M., Yu, C. ‐., Brown, L. L., Finn, D. A., Garland, T., & Crabbe, J. C. (2006) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2006.00210.x · Cited by 340 · see citing works
Alcohol-induced motor impairment caused by increased extrasynaptic GABAA receptor activity
Hanchar, H. J., Dodson, P. D., Olsen, R. W., Otis, T. S., & Wallner, M. (2005) · Nature Neuroscience · doi:10.1038/nn1398 · Cited by 306 · see citing works
GABAA receptor antagonism in the extended amygdala decreases ethanol self-administration in rats
Hyytiä, P., & Koob, G. F. (1995) · European Journal of Pharmacology · doi:10.1016/0014-2999(95)00314-b · Cited by 302 · see citing works
Comparison of prefrontal architecture and connections
Pandya, D. Ν., & Yeterian, E. H. (1996) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1996.0127 · Cited by 279 · see citing works
Distinguishing Between GABAA Receptors Responsible for Tonic and Phasic Conductances
Módy, I. (2001) · Neurochemical Research · doi:10.1023/a:1012376215967 · Cited by 261 · see citing works
Wei, W., Faria, L. C., & Módy, I. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2040-04.2004 · Cited by 242 · see citing works
Chronic Alcohol Exposure Alters Behavioral and Synaptic Plasticity of the Rodent Prefrontal Cortex
Kroener, S., Mulholland, P. J., New, N., Gass, J. T., Becker, H. C., & Chandler, L. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037541 · Cited by 236 · see citing works
Infralimbic cortex activation increases c-fos expression in intercalated neurons of the amygdala
Berretta, S., Pantazopoulos, H., Caldera, M., Pantazopoulos, P., & Paré, D. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.01.020 · Cited by 223 · see citing works
Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding
Holmes, A., Fitzgerald, P. J., MacPherson, K. P., DeBrouse, L., Colacicco, G., Flynn, S. M., Masneuf, S., Pleil, K. E., Li, C., Marcinkiewcz, C. A., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3204 · Cited by 218 · see citing works
Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking
Van den Oever, M. C., Goriounova, N. A., Wan Li, K., Van der Schors, R. C., Binnekade, R., Schoffelmeer, A. N. M., Mansvelder, H. D., Smit, A. B., Spijker, S., & De Vries, T. J. (2008) · Nature Neuroscience · doi:10.1038/nn.2165 · Cited by 206 · see citing works
ADKINS, C. E., Pillai, G. V., Kerby, J., Bonnert, T. P., Haldon, C., McKernan, R. M., González, J. E., Oades, K., Whiting, P. J., & Simpson, P. B. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104318200 · Cited by 190 · see citing works
Ethanol potentiates the GABAA-activated Cl− current in mouse hippocampal and cortical neurons
Aguayo, L. G. (1990) · European Journal of Pharmacology · doi:10.1016/0014-2999(90)90349-b · Cited by 175 · see citing works
Meinhardt, M. W., Hansson, A. C., Perreau‐Lenz, S., Bauder-Wenz, C., Stählin, O., Heilig, M. A., Harper, C. G., Drescher, K. U., Spanagel, R., & Sommer, W. H. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4062-12.2013 · Cited by 170 · see citing works
Borghese, C. M., Stórustovu, S. I., Ebert, B., Herd, M. B., Belelli, D., Lambert, J. J., Marshall, G. R., Wafford, K. A., & Harris, R. A. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.092452 · Cited by 170 · see citing works
Molecular basis for the high THIP/gaboxadol sensitivity of extrasynaptic GABAA receptors
Meera, P., Wallner, M., & Otis, T. S. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00450.2011 · Cited by 161 · see citing works
GABAA‐Receptor δ Subunit Knockout Mice Have Multiple Defects in Behavioral Responses to Ethanol
Mihalek, R., Bowers, B. J., Wehner, J. M., Kralic, J. E., VanDoren, M. J., Morrow, A. L., & Homanics, G. E. (2001) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2001.tb02179.x · Cited by 159 · see citing works
The role of prefrontal cortex D1-like and D2-like receptors in cocaine-seeking behavior in rats
Sun, W., & Rebec, G. V. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1956-x · Cited by 122 · see citing works
Boyle, A. E. L., Segal, R., Smith, B. R., & Amit, Z. (1993) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(93)90338-t · Cited by 105 · see citing works
Nowak, K., McBride, W. J., Lumeng, L., Li, T., & Murphy, J. M. (1998) · Psychopharmacology · doi:10.1007/s002130050695 · Cited by 99 · see citing works
Nie, H., Rewal, M., Gill, T. M., Dorit Ron, A., & Janak, P. H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016156108 · Cited by 90 · see citing works
Peters, J., Vallone, J., Laurendi, K., & Kalivas, P. W. (2007) · Psychopharmacology · doi:10.1007/s00213-007-1034-2 · Cited by 87 · see citing works
GABAERGIC INVOLVEMENT IN THE ACQUISITION OF VOLUNTARY ETHANOL INTAKE IN LABORATORY RATS
Smith, B. R., Robidoux, J., & Amit, Z. (1992) · Alcohol and Alcoholism · doi:10.1093/oxfordjournals.alcalc.a045234 · Cited by 83 · see citing works
Hodge, C. W., Chappelle, A. M., & Samson, H. H. (1996) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1996.tb01709.x · Cited by 77 · see citing works
Moore, E. M., & Boehm, S. L. (2009) · Behavioral Neuroscience · doi:10.1037/a0015345 · Cited by 76 · see citing works
GABAergic modulation of binge-like ethanol intake in C57BL/6J mice
Moore, E. M., Serio, K. M., Goldfarb, K. J., STEPANOVSKA, S., Linsenbardt, D. N., & Boehm, S. L. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.07.011 · Cited by 69 · see citing works
Are Extrasynaptic GABA A Receptors Important Targets for Sedative/Hypnotic Drugs?
Houston, C. M., McGee, T. P., MacKenzie, G., Troyano-Cuturi, K., Rodriguez, P. M., Kutsarova, E., Diamanti, E. M., Hosie, A. M., Franks, N. P., & Brickley, S. G. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5406-11.2012 · Cited by 68 · see citing works
Linsenbardt, D. N., & Boehm, S. L. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.08.007 · Cited by 66 · see citing works
Hodge, C. W. (1996) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)02146-9 · Cited by 53 · see citing works
Ovari, J., & Leri, F. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.08.015 · Cited by 51 · see citing works
Linsenbardt, D. N., Moore, E. M., Griffin, K. D., Gigante, E. D., & Boehm, S. L. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01459.x · Cited by 46 · see citing works
Ramaker, M. J., Ford, M. M., Fretwell, A. M., & Finn, D. A. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01551.x · Cited by 43 · see citing works
Melón, L. C., & Boehm, S. L. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.02.014 · Cited by 32 · see citing works
Täuber, M., Calame‐Droz, E., Prut, L., Rudolph, U., & Crestani, F. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02988.x · Cited by 32 · see citing works
Boyle, A. E., Smith, B. R., & Amit, Z. (1992) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(92)90491-w · Cited by 31 · see citing works
Muscimol injected into the medial prefrontal cortex of the rat alters ethanol self-administration
Samson, H. H., & Chappell, A. M. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00607-2 · Cited by 28 · see citing works
Effect of ganaxolone and THIP on operant and limited-access ethanol self-administration
Ramaker, M. J., Strong, M. N., Ford, M. M., & Finn, D. A. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.05.007 · Cited by 28 · see citing works
June, H. L., Murphy, J. M., Mellor-Burke, J. J., Lumeng, L., & Li, T. (1994) · Psychopharmacology · doi:10.1007/bf02245073 · Cited by 23 · see citing works
Groblewski, P. A., Ryabinin, A. E., & Cunningham, C. L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.09.001 · Cited by 21 · see citing works
Differences in the reinstatement of ethanol seeking with ganaxolone and gaboxadol
Ramaker, M. J., Ford, M. M., Phillips, T. J., & Finn, D. A. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.065 · Cited by 20 · see citing works
Role of Novelty and Ethanol History in Locomotor Stimulation Induced by Binge‐Like Ethanol Intake
Linsenbardt, D. N., & Boehm, S. L. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01684.x · Cited by 19 · see citing works
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- Authors
- Fritz, B. M., & Boehm II, S. L.
- Affiliations
- Indiana University Indianapolis (US)
- Corresponding author
- Fritz, Brandon M.
- ORCID
- Fritz, Brandon M.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 273
- Pages
- 8-15
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC4152776
- OpenAlex
- W2005125517
- Cited by
- 10
- References
- 62
- Citations by year
- 2023: 1 · 2022: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 1
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- PMC
- Funders
- NIAAA (AA016789, AA07462)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- gaboxadol, THIP, extrasynaptic GABAA receptors, infralimbic cortex, ethanol consumption, alcohol consumption, stress reactivity, extinction learning, behavioral flexibility, sucrose intake, C57BL/6J mice
- MeSH terms
- Alcohol Drinking, Ethanol, Animals, Isoxazoles, Male, Mice, Inbred C57BL, Microinjections, Motor Activity, Receptors, GABA-A, Prefrontal Cortex, Mice, GABA-A Receptor Agonists
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