共 51 条
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
来源:
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