title: Effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline on glutamate transporter 1 and cysteine/glutamate exchanger as well as ethanol drinking behavior in male, alcohol-preferring rats.
abstract: Alcohol consumption is largely associated with alterations in the extracellular glutamate concentrations in several brain reward regions. We recently showed that glutamate transporter 1 (GLT-1) is downregulated following chronic exposure to ethanol for 5 weeks in alcohol-preferring (P) rats and that upregulation of the GLT-1 levels in nucleus accumbens and prefrontal cortex results, in part, in attenuating ethanol consumption. Cystine glutamate antiporter (xCT) is also downregulated after chronic ethanol exposure in P rats, and its upregulation could be valuable in attenuating ethanol drinking. This study examines the effect of a synthetic compound, (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), on ethanol drinking and expressions of GLT-1 and xCT in the amygdala and the hippocampus of P rats. P rats were exposed to continuous free-choice access to water, 15% and 30% ethanol, and food for 5 weeks, after which they received treatments of MS-153 or vehicle for 5 days. The results show that MS-153 treatment significantly reduces ethanol consumption. It was revealed that GLT-1 and xCT expressions were downregulated in both the amygdala and the hippocampus of ethanol-vehicle-treated rats (ethanol-vehicle group) compared with water-control animals. MS-153 treatment upregulated GLT-1 and xCT expressions in these brain regions. These findings demonstrate an important role for MS-153 in these glutamate transporters for the attenuation of ethanol-drinking behavior.
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, Ohio.
authors.forename: Munaf
authors.initials: M
authors.lastname: Aal-Aaboda
authors.forename: Hasan
authors.initials: H
authors.lastname: Alhaddad
authors.forename: Francis
authors.initials: F
authors.lastname: Osowik
authors.forename: Surya M
authors.initials: SM
authors.lastname: Nauli
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism*; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D004326:Drinking / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009539:Nicotinic Acids / Q000627:therapeutic use*; D051381:Rats; D014404:Tubulin / Q000378:metabolism; D014803:Vitamin B Complex / Q000627:therapeutic use*; D027182:Amino Acid Transport System y+
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D002492:Central Nervous System Depressants; D000431:Ethanol; D027342:Excitatory Amino Acid Transporter 2; D009539:Nicotinic Acids; D014404:Tubulin; D014803:Vitamin B Complex; C101692:5-methyl-1-nicotinoyl-2-pyrazoline; C000723960:Slc7a11 protein, rat; D027182:Amino Acid Transport System y+
keywords: GLT-1; MS-153; amygdala; glutamate; hippocampus