The effect of mGluR5 antagonism during binge drinking on subsequent ethanol intake in C57BL/6J mice: Sex- and age-induced differences

Debra K. Cozzoli, Moriah N. Strong-Kaufman, Michelle A. Tanchuck, Joel G. Hashimoto, Kristine Wiren, Deborah (Deb) Finn

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Binge ethanol (EtOH) intake during adolescence leads to an array of behavioral and cognitive consequences including elevated intake of EtOH during adulthood, with female mice showing greater susceptibility than males. Administration of the metabotropic glutamate receptor 5 (mGluR5) antagonist 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) has been shown to reduce EtOH self-administration in adult male mice, but little is known about its effect on female and adolescent mice. Methods: MTEP (0, 10, 20 mg/kg, i.p.) was repeatedly administered to female and male, adult and adolescent C57BL/6J mice during binge sessions using the scheduled high alcohol consumption paradigm. Next, we assessed whether MTEP administration during binge altered the subsequent 24-hour EtOH intake following a period of abstinence. Finally, we investigated whether MTEP administration during binge followed by an abstinence period altered mRNA of glutamatergic genes within the nucleus accumbens of female mice. Results: MTEP significantly decreased binge EtOH intake in all mice, but only female mice exhibited altered subsequent 24-hour EtOH intake. Interestingly, the alteration in subsequent EtOH intake in female animals was age dependent, with adolescent exposure to MTEP during binge decreasing 24-hour intake and adult exposure to MTEP during binge increasing 24-hour intake. Finally, while there were no effects of MTEP pretreatment on the genes examined, there was a robust age effect found during analysis of mGluR1 (Grm1), mGluR5 (Grm5), the NR2A subunit of the NMDA receptor (Grin2a), phosphatidylinositol 3-kinase (Pik3r1), mammalian target of rapamycin (Mtor), and extracellular signal-regulated kinase (Mapk1) mRNA, with adolescent female animals having lower expression than their adult counterparts. Conclusions: Collectively, the present findings add to existing evidence implicating the contribution of long-term effects of adolescent binge drinking to enhance alcohol abuse in adulthood, while suggesting that mGluR5 antagonism may not be the best pharmacotherapy to treat binge alcohol consumption in female and adolescent animals.

Original languageEnglish (US)
Pages (from-to)730-738
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume38
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Metabotropic Glutamate 5 Receptor
Binge Drinking
Inbred C57BL Mouse
Ethanol
Animals
Alcohols
Genes
Phosphatidylinositol 3-Kinase
Drug therapy
Alcohol Drinking
Messenger RNA
Extracellular Signal-Regulated MAP Kinases
Sirolimus
N-Methyl-D-Aspartate Receptors
Excitatory Amino Acid Antagonists
Metabotropic Glutamate Receptors
Self Administration
Nucleus Accumbens
Alcoholism
Drug Therapy

Keywords

  • Adolescent
  • Adult
  • Alcohol
  • Glutamate
  • MTEP

ASJC Scopus subject areas

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

Cite this

The effect of mGluR5 antagonism during binge drinking on subsequent ethanol intake in C57BL/6J mice : Sex- and age-induced differences. / Cozzoli, Debra K.; Strong-Kaufman, Moriah N.; Tanchuck, Michelle A.; Hashimoto, Joel G.; Wiren, Kristine; Finn, Deborah (Deb).

In: Alcoholism: Clinical and Experimental Research, Vol. 38, No. 3, 2014, p. 730-738.

Research output: Contribution to journalArticle

@article{0641924a13854fab8840a517216c995d,
title = "The effect of mGluR5 antagonism during binge drinking on subsequent ethanol intake in C57BL/6J mice: Sex- and age-induced differences",
abstract = "Background: Binge ethanol (EtOH) intake during adolescence leads to an array of behavioral and cognitive consequences including elevated intake of EtOH during adulthood, with female mice showing greater susceptibility than males. Administration of the metabotropic glutamate receptor 5 (mGluR5) antagonist 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) has been shown to reduce EtOH self-administration in adult male mice, but little is known about its effect on female and adolescent mice. Methods: MTEP (0, 10, 20 mg/kg, i.p.) was repeatedly administered to female and male, adult and adolescent C57BL/6J mice during binge sessions using the scheduled high alcohol consumption paradigm. Next, we assessed whether MTEP administration during binge altered the subsequent 24-hour EtOH intake following a period of abstinence. Finally, we investigated whether MTEP administration during binge followed by an abstinence period altered mRNA of glutamatergic genes within the nucleus accumbens of female mice. Results: MTEP significantly decreased binge EtOH intake in all mice, but only female mice exhibited altered subsequent 24-hour EtOH intake. Interestingly, the alteration in subsequent EtOH intake in female animals was age dependent, with adolescent exposure to MTEP during binge decreasing 24-hour intake and adult exposure to MTEP during binge increasing 24-hour intake. Finally, while there were no effects of MTEP pretreatment on the genes examined, there was a robust age effect found during analysis of mGluR1 (Grm1), mGluR5 (Grm5), the NR2A subunit of the NMDA receptor (Grin2a), phosphatidylinositol 3-kinase (Pik3r1), mammalian target of rapamycin (Mtor), and extracellular signal-regulated kinase (Mapk1) mRNA, with adolescent female animals having lower expression than their adult counterparts. Conclusions: Collectively, the present findings add to existing evidence implicating the contribution of long-term effects of adolescent binge drinking to enhance alcohol abuse in adulthood, while suggesting that mGluR5 antagonism may not be the best pharmacotherapy to treat binge alcohol consumption in female and adolescent animals.",
keywords = "Adolescent, Adult, Alcohol, Glutamate, MTEP",
author = "Cozzoli, {Debra K.} and Strong-Kaufman, {Moriah N.} and Tanchuck, {Michelle A.} and Hashimoto, {Joel G.} and Kristine Wiren and Finn, {Deborah (Deb)}",
year = "2014",
doi = "10.1111/acer.12292",
language = "English (US)",
volume = "38",
pages = "730--738",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - The effect of mGluR5 antagonism during binge drinking on subsequent ethanol intake in C57BL/6J mice

T2 - Sex- and age-induced differences

AU - Cozzoli, Debra K.

AU - Strong-Kaufman, Moriah N.

AU - Tanchuck, Michelle A.

AU - Hashimoto, Joel G.

AU - Wiren, Kristine

AU - Finn, Deborah (Deb)

PY - 2014

Y1 - 2014

N2 - Background: Binge ethanol (EtOH) intake during adolescence leads to an array of behavioral and cognitive consequences including elevated intake of EtOH during adulthood, with female mice showing greater susceptibility than males. Administration of the metabotropic glutamate receptor 5 (mGluR5) antagonist 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) has been shown to reduce EtOH self-administration in adult male mice, but little is known about its effect on female and adolescent mice. Methods: MTEP (0, 10, 20 mg/kg, i.p.) was repeatedly administered to female and male, adult and adolescent C57BL/6J mice during binge sessions using the scheduled high alcohol consumption paradigm. Next, we assessed whether MTEP administration during binge altered the subsequent 24-hour EtOH intake following a period of abstinence. Finally, we investigated whether MTEP administration during binge followed by an abstinence period altered mRNA of glutamatergic genes within the nucleus accumbens of female mice. Results: MTEP significantly decreased binge EtOH intake in all mice, but only female mice exhibited altered subsequent 24-hour EtOH intake. Interestingly, the alteration in subsequent EtOH intake in female animals was age dependent, with adolescent exposure to MTEP during binge decreasing 24-hour intake and adult exposure to MTEP during binge increasing 24-hour intake. Finally, while there were no effects of MTEP pretreatment on the genes examined, there was a robust age effect found during analysis of mGluR1 (Grm1), mGluR5 (Grm5), the NR2A subunit of the NMDA receptor (Grin2a), phosphatidylinositol 3-kinase (Pik3r1), mammalian target of rapamycin (Mtor), and extracellular signal-regulated kinase (Mapk1) mRNA, with adolescent female animals having lower expression than their adult counterparts. Conclusions: Collectively, the present findings add to existing evidence implicating the contribution of long-term effects of adolescent binge drinking to enhance alcohol abuse in adulthood, while suggesting that mGluR5 antagonism may not be the best pharmacotherapy to treat binge alcohol consumption in female and adolescent animals.

AB - Background: Binge ethanol (EtOH) intake during adolescence leads to an array of behavioral and cognitive consequences including elevated intake of EtOH during adulthood, with female mice showing greater susceptibility than males. Administration of the metabotropic glutamate receptor 5 (mGluR5) antagonist 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) has been shown to reduce EtOH self-administration in adult male mice, but little is known about its effect on female and adolescent mice. Methods: MTEP (0, 10, 20 mg/kg, i.p.) was repeatedly administered to female and male, adult and adolescent C57BL/6J mice during binge sessions using the scheduled high alcohol consumption paradigm. Next, we assessed whether MTEP administration during binge altered the subsequent 24-hour EtOH intake following a period of abstinence. Finally, we investigated whether MTEP administration during binge followed by an abstinence period altered mRNA of glutamatergic genes within the nucleus accumbens of female mice. Results: MTEP significantly decreased binge EtOH intake in all mice, but only female mice exhibited altered subsequent 24-hour EtOH intake. Interestingly, the alteration in subsequent EtOH intake in female animals was age dependent, with adolescent exposure to MTEP during binge decreasing 24-hour intake and adult exposure to MTEP during binge increasing 24-hour intake. Finally, while there were no effects of MTEP pretreatment on the genes examined, there was a robust age effect found during analysis of mGluR1 (Grm1), mGluR5 (Grm5), the NR2A subunit of the NMDA receptor (Grin2a), phosphatidylinositol 3-kinase (Pik3r1), mammalian target of rapamycin (Mtor), and extracellular signal-regulated kinase (Mapk1) mRNA, with adolescent female animals having lower expression than their adult counterparts. Conclusions: Collectively, the present findings add to existing evidence implicating the contribution of long-term effects of adolescent binge drinking to enhance alcohol abuse in adulthood, while suggesting that mGluR5 antagonism may not be the best pharmacotherapy to treat binge alcohol consumption in female and adolescent animals.

KW - Adolescent

KW - Adult

KW - Alcohol

KW - Glutamate

KW - MTEP

UR - http://www.scopus.com/inward/record.url?scp=84896262797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896262797&partnerID=8YFLogxK

U2 - 10.1111/acer.12292

DO - 10.1111/acer.12292

M3 - Article

C2 - 27695144

AN - SCOPUS:84896262797

VL - 38

SP - 730

EP - 738

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 3

ER -