Contributed equally to the work.
The Effect of mGluR5 Antagonism During Binge Drinking on Subsequent Ethanol Intake in C57BL/6J Mice: Sex- and Age-Induced Differences
Article first published online: 29 OCT 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 38, Issue 3, pages 730–738, March 2014
How to Cite
Cozzoli, D. K., Strong-Kaufman, M. N., Tanchuck, M. A., Hashimoto, J. G., Wiren, K. M. and Finn, D. A. (2014), The Effect of mGluR5 Antagonism During Binge Drinking on Subsequent Ethanol Intake in C57BL/6J Mice: Sex- and Age-Induced Differences. Alcoholism: Clinical and Experimental Research, 38: 730–738. doi: 10.1111/acer.12292
- Issue published online: 15 MAR 2014
- Article first published online: 29 OCT 2013
- Manuscript Accepted: 28 AUG 2013
- Manuscript Received: 4 JUN 2013
- Department of Veterans Affairs. Grant Number: T32 AA007468
- MTEP ;
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.
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.
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.
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.