EFFECTS OF AMPICILLIN, CEFAZOLIN AND CEFOPERAZONE TREATMENTS ON GLT-1 EXPRESSIONS IN THE MESOCORTICOLIMBIC SYSTEM AND ETHANOL INTAKE IN ALCOHOL-PREFERRING RATS

被引:43
作者
Rao, P. S. S. [1 ]
Goodwani, S. [1 ]
Bell, R. L. [3 ]
Wei, Y. [2 ]
Boddu, S. H. S. [2 ]
Sari, Y. [1 ]
机构
[1] Univ Toledo, Coll Pharm & Pharmaceut Sci, Dept Pharmacol, Toledo, OH 43614 USA
[2] Univ Toledo, Coll Pharm & Pharmaceut Sci, Dept Pharm Practice, Toledo, OH 43614 USA
[3] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA
关键词
cefazolin; cefoperazone; ampicillin; glutamate; alcohol intake; EAAT2; BETA-LACTAM ANTIBIOTICS; GLUTAMATE TRANSPORTER EXPRESSION; COCAINE-SEEKING BEHAVIOR; NUCLEUS-ACCUMBENS; EXTRACELLULAR GLUTAMATE; UP-REGULATION; P RATS; PREFRONTAL CORTEX; DRINKING BEHAVIOR; DRUG-ADDICTION;
D O I
10.1016/j.neuroscience.2015.03.038
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Chronic ethanol consumption is known to downregulate expression of the major glutamate transporter 1 (GLT-1), which increases extracellular glutamate concentrations in subregions of the mesocorticolimbic reward pathway. While beta-lactam antibiotics were initially identified as potent upregulators of GLT-1 expression, only ceftriaxone has been extensively studied in various drug addiction models. Therefore, in this study, adult male alcohol-preferring (P) rats exposed chronically to ethanol were treated with other beta-lactam antibiotics, ampicillin, cefazolin or cefoperazone (100 mg/kg) once daily for five consecutive days to assess their effects on ethanol consumption. The results demonstrated that each compound significantly reduced ethanol intake compared to the saline-treated control group. Importantly, each compound significantly upregulated both GLT-1 and pAKT expressions in the nucleus accumbens and prefrontal cortex compared to saline-treated control group. In addition, only cefoperazone significantly inhibited hepatic aldehyde dehydrogenase-2 enzyme activity. Moreover, these beta-lactams exerted only a transient effect on sucrose drinking, suggesting specificity for chronically inhibiting ethanol reward in adult male P rats. Cerebrospinal fluid concentrations of ampicillin, cefazolin or cefoperazone have been confirmed using high-performance liquid chromatography. These findings demonstrate that multiple beta-lactam antibiotics demonstrate efficacy in reducing alcohol consumption and appear to be potential therapeutic compounds for treating alcohol abuse and/or dependence. In addition, these results suggest that pAKT may be an important player in this effect, possibly through increased transcription of GLT-1. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:164 / 174
页数:11
相关论文
共 51 条
[1]   Attenuation of Ethanol Withdrawal by Ceftriaxone-Induced Upregulation of Glutamate Transporter EAAT2 [J].
Abulseoud, Osama A. ;
Camsari, Ulas M. ;
Ruby, Christina L. ;
Kasasbeh, Aimen ;
Choi, Sun ;
Choi, Doo-Sup .
NEUROPSYCHOPHARMACOLOGY, 2014, 39 (07) :1674-1684
[2]   Ceftriaxone upregulates the glutamate transporter in medial prefrontal cortex and blocks reinstatement of methamphetamine seeking in a condition place preference paradigm [J].
Abulseoud, Osama A. ;
Miller, Joseph D. ;
Wu, Jinhua ;
Choi, Doo-Sup ;
Holschneider, Daniel P. .
BRAIN RESEARCH, 2012, 1456 :14-21
[3]   Effects of MS-153 on chronic ethanol consumption and GLT1 modulation of glutamate levels in male alcohol-preferring rats [J].
Alhaddad, Hasan ;
Kim, Nathaniel T. ;
Aal-Aaboda, Munaf ;
Althobaiti, Yusuf S. ;
Leighton, James ;
Boddu, Sai H. S. ;
Wei, Yangjie ;
Sari, Youssef .
FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 2014, 8
[4]   Effects of ceftriaxone on ethanol intake: a possible role for xCT and GLT-1 isoforms modulation of glutamate levels in P rats [J].
Alhaddad, Hasan ;
Das, Sujan C. ;
Sari, Youssef .
PSYCHOPHARMACOLOGY, 2014, 231 (20) :4049-4057
[5]   Effects of short deprivation and re-exposure intervals on the ethanol drinking behavior of selectively bred high alcohol-consuming rats [J].
Bell, Richard L. ;
Rodd, Zachary A. ;
Schultz, Jonathon A. ;
Peper, Caron L. ;
Lumeng, Lawrence ;
Murphy, James M. ;
McBride, William J. .
ALCOHOL, 2008, 42 (05) :407-416
[6]   Simultaneous determination of unbound cefoperazone in rat blood and brain using microdialysis [J].
Chang, YL ;
Chou, MH ;
Lin, MF ;
Chen, YF ;
Chen, CF ;
Cheng, FC ;
Tsai, TH .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2000, 52 (08) :963-968
[7]   AMOXICILLIN ENTRY INTO HUMAN CEREBROSPINAL-FLUID - COMPARISON WITH AMPICILLIN [J].
CLUMECK, N ;
THYS, JP ;
VANHOOF, R ;
VANDERLINDEN, MP ;
BUTZLER, JP ;
YOURASSOWSKY, E .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1978, 14 (04) :531-532
[8]   Alcohol drinking and deprivation alter basal extracellular glutamate concentrations and clearance in the mesolimbic system of alcohol-preferring (P) rats [J].
Ding, Zheng-Ming ;
Rodd, Zachary A. ;
Engleman, Eric A. ;
Bailey, Jason A. ;
Lahiri, Debomoy K. ;
McBride, William J. .
ADDICTION BIOLOGY, 2013, 18 (02) :297-306
[9]   Role of the Major Glutamate Transporter GLT1 in Nucleus Accumbens Core Versus Shell in Cue-Induced Cocaine-Seeking Behavior [J].
Fischer, Kathryn D. ;
Houston, Alexander C. W. ;
Rebec, George V. .
JOURNAL OF NEUROSCIENCE, 2013, 33 (22) :9319-9327
[10]   FERROUS SULFATE COMBINED WITH ASCORBIC-ACID DOES NOT SIGNIFICANTLY REDUCE ACETALDEHYDE ACCUMULATION IN THE BLOOD OF ALCOHOLIZED RATS TREATED WITH DISULFIRAM OR BETA-LACTAM ANTIBIOTICS [J].
FREUNDT, KJ ;
HEILER, C ;
SCHREINER, E .
ALCOHOL, 1990, 7 (04) :295-298