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Differential Effects of Chronic Ethanol Consumption and Withdrawal on Homer/Glutamate Receptor Expression in Subregions of the Accumbens and Amygdala of P Rats

Authors

  • Ilona Obara,

    1. From the Department of Psychology and the Neuroscience Research Institute (IO, SPG, CMR, AWA, KKS), University of California at Santa Barbara, Santa Barbara, California; Department of Pain Pharmacology (IO), Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland; and Department of Psychiatry (RLB, LAL, WAT), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
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  • Richard L. Bell,

    1. From the Department of Psychology and the Neuroscience Research Institute (IO, SPG, CMR, AWA, KKS), University of California at Santa Barbara, Santa Barbara, California; Department of Pain Pharmacology (IO), Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland; and Department of Psychiatry (RLB, LAL, WAT), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
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  • Scott P. Goulding,

    1. From the Department of Psychology and the Neuroscience Research Institute (IO, SPG, CMR, AWA, KKS), University of California at Santa Barbara, Santa Barbara, California; Department of Pain Pharmacology (IO), Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland; and Department of Psychiatry (RLB, LAL, WAT), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
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  • Cindy M. Reyes,

    1. From the Department of Psychology and the Neuroscience Research Institute (IO, SPG, CMR, AWA, KKS), University of California at Santa Barbara, Santa Barbara, California; Department of Pain Pharmacology (IO), Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland; and Department of Psychiatry (RLB, LAL, WAT), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
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  • Lindsay A. Larson,

    1. From the Department of Psychology and the Neuroscience Research Institute (IO, SPG, CMR, AWA, KKS), University of California at Santa Barbara, Santa Barbara, California; Department of Pain Pharmacology (IO), Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland; and Department of Psychiatry (RLB, LAL, WAT), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
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  • Alexis W. Ary,

    1. From the Department of Psychology and the Neuroscience Research Institute (IO, SPG, CMR, AWA, KKS), University of California at Santa Barbara, Santa Barbara, California; Department of Pain Pharmacology (IO), Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland; and Department of Psychiatry (RLB, LAL, WAT), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
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  • William A. Truitt,

    1. From the Department of Psychology and the Neuroscience Research Institute (IO, SPG, CMR, AWA, KKS), University of California at Santa Barbara, Santa Barbara, California; Department of Pain Pharmacology (IO), Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland; and Department of Psychiatry (RLB, LAL, WAT), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
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  • Karen K. Szumlinski

    1. From the Department of Psychology and the Neuroscience Research Institute (IO, SPG, CMR, AWA, KKS), University of California at Santa Barbara, Santa Barbara, California; Department of Pain Pharmacology (IO), Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland; and Department of Psychiatry (RLB, LAL, WAT), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
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Reprint requests: Karen K. Szumlinski, PhD, Department of Psychology, University of California at Santa Barbara, Santa Barbara, CA 93106-9660; Fax: 1-805-893-4303; E-mail: szumlinski@psych.ucsb.edu

Abstract

Background:  Homer proteins are constituents of scaffolding complexes that regulate the trafficking and function of central Group1 metabotropic glutamate receptors (mGluRs) and N-methyl-d-aspartate (NMDA) receptors. Research supports the involvement of these proteins in ethanol-induced neuroplasticity in mouse. In this study, we examined the effects of short versus long-term withdrawal from chronic ethanol consumption on Homer and glutamate receptor protein expression within striatal and amygdala subregions of selectively bred, alcohol-preferring P rats.

Methods:  For 6 months, male P rats had concurrent access to 15% and 30% ethanol solutions under intermittent (IA: 4 d/wk) or continuous (CA: 7 d/wk) access conditions in their home cage. Rats were killed 24 hours (short withdrawal: SW) or 4 weeks (long withdrawal: LW) after termination of ethanol access, subregions of interest were micropunched and tissue processed for detection of Group1 mGluRs, NR2 subunits of the NMDA receptor and Homer protein expression.

Results:  Within the nucleus accumbens (NAC), limited changes in NR2a and NR2b expression were detected in the shell (NACsh), whereas substantial changes were observed for Homer2a/b, mGluRs as well as NR2a and NR2b subunits in the core (NACc). Within the amygdala, no changes were detected in the basolateral subregion, whereas substantial changes, many paralleling those observed in the NACc, were detected in the central nucleus (CeA) subregion. In addition, most of the changes observed in the CeA, but not NACc, were present in both SW and LW rats.

Conclusions:  Overall, these subregion specific, ethanol-induced increases in mGluR/Homer2/NR2 expression within the NAC and amygdala suggest changes in glutamatergic plasticity had taken place. This may be a result of learning and subsequent memory formation of ethanol’s rewarding effects in these brain structures, which may, in part, mediate the chronic relapsing nature of alcohol abuse.

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