Tags

Type your tag names separated by a space and hit enter

The metabotropic glutamate 5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine reduces ethanol self-administration in multiple strains of alcohol-preferring rats and regulates olfactory glutamatergic systems.
J Pharmacol Exp Ther. 2005 Nov; 315(2):590-600.JP

Abstract

The metabotropic glutamate 5 receptor (mGlu5) receptor has been implicated as having a role in pain modulation, anxiety, and depression, as well as drug-seeking behavior. In the present study, we examined the effect of the selective mGlu5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) on operant ethanol self-administration by two strains of rats, the Fawn-Hooded (FH) rat and the inbred alcohol-preferring (iP) rat. MTEP (2 mg/kg i.p.) caused a significant reduction in responding for ethanol by both strains of rats; however, in the iP rats, MTEP also induced apparent sedation at this dose, although still reduced alcohol responding at lower doses. Chronic MTEP (2 mg/kg/day) caused a significant reduction in ethanol consumption by FH rats in a two-bottle preference test; however, chronic treatment with this dose had no effect on anxiety-like behavior or depressive-like behavior in FH rats, suggesting the dose used was subthreshold for anxiolytic or antidepressive-like effects. Finally, repeated dosing with MTEP (2 mg/kg i.p.) caused significant reductions in expression of the mRNA encoding the NR1 subunit of the N-methyl-D-aspartate receptor and the GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor in the cingulate cortex. A significant decrease in NR1 expression also occurred in the piriform cortex. Chronic MTEP also caused a significant decrease in mGlu5 gene expression and a significant increase in dopamine transporter and dopamine D(2)-like receptor binding within the olfactory tubercle. Collectively, these data suggest that MTEP can reduce alcohol-seeking behavior in different rodent models of alcoholism, and this effect is associated with regulation of cortical glutamate systems, particularly those in olfactory-related regions.

Authors+Show Affiliations

Howard Florey Institute, Royal Parade, University of Melbourne, Victoria, Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16014750

Citation

Cowen, Michael S., et al. "The Metabotropic Glutamate 5 Receptor Antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine Reduces Ethanol Self-administration in Multiple Strains of Alcohol-preferring Rats and Regulates Olfactory Glutamatergic Systems." The Journal of Pharmacology and Experimental Therapeutics, vol. 315, no. 2, 2005, pp. 590-600.
Cowen MS, Djouma E, Lawrence AJ. The metabotropic glutamate 5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine reduces ethanol self-administration in multiple strains of alcohol-preferring rats and regulates olfactory glutamatergic systems. J Pharmacol Exp Ther. 2005;315(2):590-600.
Cowen, M. S., Djouma, E., & Lawrence, A. J. (2005). The metabotropic glutamate 5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine reduces ethanol self-administration in multiple strains of alcohol-preferring rats and regulates olfactory glutamatergic systems. The Journal of Pharmacology and Experimental Therapeutics, 315(2), 590-600.
Cowen MS, Djouma E, Lawrence AJ. The Metabotropic Glutamate 5 Receptor Antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine Reduces Ethanol Self-administration in Multiple Strains of Alcohol-preferring Rats and Regulates Olfactory Glutamatergic Systems. J Pharmacol Exp Ther. 2005;315(2):590-600. PubMed PMID: 16014750.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The metabotropic glutamate 5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine reduces ethanol self-administration in multiple strains of alcohol-preferring rats and regulates olfactory glutamatergic systems. AU - Cowen,Michael S, AU - Djouma,Elvan, AU - Lawrence,Andrew J, Y1 - 2005/07/13/ PY - 2005/7/15/pubmed PY - 2006/1/13/medline PY - 2005/7/15/entrez SP - 590 EP - 600 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 315 IS - 2 N2 - The metabotropic glutamate 5 receptor (mGlu5) receptor has been implicated as having a role in pain modulation, anxiety, and depression, as well as drug-seeking behavior. In the present study, we examined the effect of the selective mGlu5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) on operant ethanol self-administration by two strains of rats, the Fawn-Hooded (FH) rat and the inbred alcohol-preferring (iP) rat. MTEP (2 mg/kg i.p.) caused a significant reduction in responding for ethanol by both strains of rats; however, in the iP rats, MTEP also induced apparent sedation at this dose, although still reduced alcohol responding at lower doses. Chronic MTEP (2 mg/kg/day) caused a significant reduction in ethanol consumption by FH rats in a two-bottle preference test; however, chronic treatment with this dose had no effect on anxiety-like behavior or depressive-like behavior in FH rats, suggesting the dose used was subthreshold for anxiolytic or antidepressive-like effects. Finally, repeated dosing with MTEP (2 mg/kg i.p.) caused significant reductions in expression of the mRNA encoding the NR1 subunit of the N-methyl-D-aspartate receptor and the GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor in the cingulate cortex. A significant decrease in NR1 expression also occurred in the piriform cortex. Chronic MTEP also caused a significant decrease in mGlu5 gene expression and a significant increase in dopamine transporter and dopamine D(2)-like receptor binding within the olfactory tubercle. Collectively, these data suggest that MTEP can reduce alcohol-seeking behavior in different rodent models of alcoholism, and this effect is associated with regulation of cortical glutamate systems, particularly those in olfactory-related regions. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16014750/The_metabotropic_glutamate_5_receptor_antagonist_3_[_2_methyl_13_thiazol_4_yl_ethynyl]_pyridine_reduces_ethanol_self_administration_in_multiple_strains_of_alcohol_preferring_rats_and_regulates_olfactory_glutamatergic_systems_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16014750 DB - PRIME DP - Unbound Medicine ER -