Differential effects of chronic ethanol consumption and withdrawal on homer/glutamate receptor expression in subregions of the accumbens and amygdala of p rats

Ilona Obara, Richard Bell, Scott P. Goulding, Cindy M. Reyes, Lindsay A. Larson, Alexis W. Ary, William Truitt, Karen K. Szumlinski

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1924-1934
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume33
Issue number11
DOIs
StatePublished - Nov 2009

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Glutamate Receptors
Amygdala
Rats
Ethanol
Metabotropic Glutamate Receptors
Nucleus Accumbens
Proteins
Alcohols
Corpus Striatum
Neuronal Plasticity
Alcoholism
Plasticity
Brain
Learning
Tissue
Data storage equipment
Research

Keywords

  • Amygdala
  • Ethanol Consumption
  • Group1 Metabotropic Glutamate Receptors
  • Homer Proteins
  • NMDA Receptors
  • Nucleus Accumbens

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

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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. / Obara, Ilona; Bell, Richard; Goulding, Scott P.; Reyes, Cindy M.; Larson, Lindsay A.; Ary, Alexis W.; Truitt, William; Szumlinski, Karen K.

In: Alcoholism: Clinical and Experimental Research, Vol. 33, No. 11, 11.2009, p. 1924-1934.

Research output: Contribution to journalArticle

Obara, Ilona ; Bell, Richard ; Goulding, Scott P. ; Reyes, Cindy M. ; Larson, Lindsay A. ; Ary, Alexis W. ; Truitt, William ; Szumlinski, Karen K. / Differential effects of chronic ethanol consumption and withdrawal on homer/glutamate receptor expression in subregions of the accumbens and amygdala of p rats. In: Alcoholism: Clinical and Experimental Research. 2009 ; Vol. 33, No. 11. pp. 1924-1934.
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AU - Bell, Richard

AU - Goulding, Scott P.

AU - Reyes, Cindy M.

AU - Larson, Lindsay A.

AU - Ary, Alexis W.

AU - Truitt, William

AU - Szumlinski, Karen K.

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N2 - 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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