Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats

Arshad Haider, Nicholas C. Woodward, Kevin D. Lominac, Arianne D. Sacramento, Matthias Klugmann, Richard Bell, Karen K. Szumlinski

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In murine models of alcoholism, the glutamate receptor scaffolding protein Homer2 bidirectionally regulates alcohol intake. Although chronic alcohol drinking increases Homer2 expression within the core subregion of the nucleus accumbens (NAc) of alcohol-preferring P rats, the relevance of this neuroadaptation for alcohol intake has yet to be determined in rats. Thus, the present study employed an adeno-associated viral vector (AAV) strategy to over-express and knock down the major rodent isoform Homer2b within the NAc of both P and outbred Wistar rats to examine for changes in alcohol preference and intake (0-30% v/v) under continuous-access procedures. The generalization of AAV effects to non-drug, palatable, sweet solutions was also determined in tests of sucrose (0-5% w/v) and saccharin (0-0.125% w/v) intake/preference. No net-flux invivo microdialysis was conducted for glutamate in the NAc to relate Homer2-dependent changes in alcohol intake to extracellular levels of glutamate. Line differences were noted for sweet solution preference and intake, but these variables were not affected by intra-NAc AAV infusion in either line. In contrast, Homer2b over-expression elevated, while Homer2b knock-down reduced, alcohol intake in both lines, and this effect was greatest at the highest concentration. Strikingly, in P rats there was a direct association between changes in Homer2b expression and NAc extracellular glutamate levels, but this effect was not seen in Wistar rats. These data indicate that NAc Homer2b expression actively regulates alcohol consumption by rats, paralleling this previous observation in mice. Overall, these findings underscore the importance of mesocorticolimbic glutamate activity in alcohol abuse/dependence and suggest that Homer2b and/or its constituents may serve as molecular targets for the treatment of these disorders.

Original languageEnglish
Pages (from-to)533-542
Number of pages10
JournalAlcohol
Volume49
Issue number6
DOIs
StatePublished - Sep 1 2015

Fingerprint

Nucleus Accumbens
Wistar Rats
Rats
alcohol
Alcohols
Glutamic Acid
Alcoholism
Alcohol Drinking
Saccharin
Microdialysis
Glutamate Receptors
Sucrose
Rodentia
Protein Isoforms
alcohol consumption
Observation
alcoholism
abuse
Fluxes
Proteins

Keywords

  • AAV
  • Alcohol preference
  • Glutamate
  • Homer2
  • Nucleus accumbens
  • P rat

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neurology
  • Toxicology
  • Health(social science)

Cite this

Haider, A., Woodward, N. C., Lominac, K. D., Sacramento, A. D., Klugmann, M., Bell, R., & Szumlinski, K. K. (2015). Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats. Alcohol, 49(6), 533-542. https://doi.org/10.1016/j.alcohol.2015.03.009

Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats. / Haider, Arshad; Woodward, Nicholas C.; Lominac, Kevin D.; Sacramento, Arianne D.; Klugmann, Matthias; Bell, Richard; Szumlinski, Karen K.

In: Alcohol, Vol. 49, No. 6, 01.09.2015, p. 533-542.

Research output: Contribution to journalArticle

Haider, A, Woodward, NC, Lominac, KD, Sacramento, AD, Klugmann, M, Bell, R & Szumlinski, KK 2015, 'Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats', Alcohol, vol. 49, no. 6, pp. 533-542. https://doi.org/10.1016/j.alcohol.2015.03.009
Haider, Arshad ; Woodward, Nicholas C. ; Lominac, Kevin D. ; Sacramento, Arianne D. ; Klugmann, Matthias ; Bell, Richard ; Szumlinski, Karen K. / Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats. In: Alcohol. 2015 ; Vol. 49, No. 6. pp. 533-542.
@article{242e17ca1893447495f26528ca8b3276,
title = "Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats",
abstract = "In murine models of alcoholism, the glutamate receptor scaffolding protein Homer2 bidirectionally regulates alcohol intake. Although chronic alcohol drinking increases Homer2 expression within the core subregion of the nucleus accumbens (NAc) of alcohol-preferring P rats, the relevance of this neuroadaptation for alcohol intake has yet to be determined in rats. Thus, the present study employed an adeno-associated viral vector (AAV) strategy to over-express and knock down the major rodent isoform Homer2b within the NAc of both P and outbred Wistar rats to examine for changes in alcohol preference and intake (0-30{\%} v/v) under continuous-access procedures. The generalization of AAV effects to non-drug, palatable, sweet solutions was also determined in tests of sucrose (0-5{\%} w/v) and saccharin (0-0.125{\%} w/v) intake/preference. No net-flux invivo microdialysis was conducted for glutamate in the NAc to relate Homer2-dependent changes in alcohol intake to extracellular levels of glutamate. Line differences were noted for sweet solution preference and intake, but these variables were not affected by intra-NAc AAV infusion in either line. In contrast, Homer2b over-expression elevated, while Homer2b knock-down reduced, alcohol intake in both lines, and this effect was greatest at the highest concentration. Strikingly, in P rats there was a direct association between changes in Homer2b expression and NAc extracellular glutamate levels, but this effect was not seen in Wistar rats. These data indicate that NAc Homer2b expression actively regulates alcohol consumption by rats, paralleling this previous observation in mice. Overall, these findings underscore the importance of mesocorticolimbic glutamate activity in alcohol abuse/dependence and suggest that Homer2b and/or its constituents may serve as molecular targets for the treatment of these disorders.",
keywords = "AAV, Alcohol preference, Glutamate, Homer2, Nucleus accumbens, P rat",
author = "Arshad Haider and Woodward, {Nicholas C.} and Lominac, {Kevin D.} and Sacramento, {Arianne D.} and Matthias Klugmann and Richard Bell and Szumlinski, {Karen K.}",
year = "2015",
month = "9",
day = "1",
doi = "10.1016/j.alcohol.2015.03.009",
language = "English",
volume = "49",
pages = "533--542",
journal = "Alcohol",
issn = "0741-8329",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats

AU - Haider, Arshad

AU - Woodward, Nicholas C.

AU - Lominac, Kevin D.

AU - Sacramento, Arianne D.

AU - Klugmann, Matthias

AU - Bell, Richard

AU - Szumlinski, Karen K.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - In murine models of alcoholism, the glutamate receptor scaffolding protein Homer2 bidirectionally regulates alcohol intake. Although chronic alcohol drinking increases Homer2 expression within the core subregion of the nucleus accumbens (NAc) of alcohol-preferring P rats, the relevance of this neuroadaptation for alcohol intake has yet to be determined in rats. Thus, the present study employed an adeno-associated viral vector (AAV) strategy to over-express and knock down the major rodent isoform Homer2b within the NAc of both P and outbred Wistar rats to examine for changes in alcohol preference and intake (0-30% v/v) under continuous-access procedures. The generalization of AAV effects to non-drug, palatable, sweet solutions was also determined in tests of sucrose (0-5% w/v) and saccharin (0-0.125% w/v) intake/preference. No net-flux invivo microdialysis was conducted for glutamate in the NAc to relate Homer2-dependent changes in alcohol intake to extracellular levels of glutamate. Line differences were noted for sweet solution preference and intake, but these variables were not affected by intra-NAc AAV infusion in either line. In contrast, Homer2b over-expression elevated, while Homer2b knock-down reduced, alcohol intake in both lines, and this effect was greatest at the highest concentration. Strikingly, in P rats there was a direct association between changes in Homer2b expression and NAc extracellular glutamate levels, but this effect was not seen in Wistar rats. These data indicate that NAc Homer2b expression actively regulates alcohol consumption by rats, paralleling this previous observation in mice. Overall, these findings underscore the importance of mesocorticolimbic glutamate activity in alcohol abuse/dependence and suggest that Homer2b and/or its constituents may serve as molecular targets for the treatment of these disorders.

AB - In murine models of alcoholism, the glutamate receptor scaffolding protein Homer2 bidirectionally regulates alcohol intake. Although chronic alcohol drinking increases Homer2 expression within the core subregion of the nucleus accumbens (NAc) of alcohol-preferring P rats, the relevance of this neuroadaptation for alcohol intake has yet to be determined in rats. Thus, the present study employed an adeno-associated viral vector (AAV) strategy to over-express and knock down the major rodent isoform Homer2b within the NAc of both P and outbred Wistar rats to examine for changes in alcohol preference and intake (0-30% v/v) under continuous-access procedures. The generalization of AAV effects to non-drug, palatable, sweet solutions was also determined in tests of sucrose (0-5% w/v) and saccharin (0-0.125% w/v) intake/preference. No net-flux invivo microdialysis was conducted for glutamate in the NAc to relate Homer2-dependent changes in alcohol intake to extracellular levels of glutamate. Line differences were noted for sweet solution preference and intake, but these variables were not affected by intra-NAc AAV infusion in either line. In contrast, Homer2b over-expression elevated, while Homer2b knock-down reduced, alcohol intake in both lines, and this effect was greatest at the highest concentration. Strikingly, in P rats there was a direct association between changes in Homer2b expression and NAc extracellular glutamate levels, but this effect was not seen in Wistar rats. These data indicate that NAc Homer2b expression actively regulates alcohol consumption by rats, paralleling this previous observation in mice. Overall, these findings underscore the importance of mesocorticolimbic glutamate activity in alcohol abuse/dependence and suggest that Homer2b and/or its constituents may serve as molecular targets for the treatment of these disorders.

KW - AAV

KW - Alcohol preference

KW - Glutamate

KW - Homer2

KW - Nucleus accumbens

KW - P rat

UR - http://www.scopus.com/inward/record.url?scp=84940450830&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940450830&partnerID=8YFLogxK

U2 - 10.1016/j.alcohol.2015.03.009

DO - 10.1016/j.alcohol.2015.03.009

M3 - Article

C2 - 26254965

AN - SCOPUS:84940450830

VL - 49

SP - 533

EP - 542

JO - Alcohol

JF - Alcohol

SN - 0741-8329

IS - 6

ER -