1.
Neuroscience. 2015 Jun 4;295:164-74. doi: 10.1016/j.neuroscience.2015.03.038. Epub 2015 Mar 24.

Effects of ampicillin, cefazolin and cefoperazone treatments on GLT-1 expressions in the mesocorticolimbic system and ethanol intake in alcohol-preferring rats.

Author information

1
University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology, Toledo, OH, USA.
2
Indiana University School of Medicine, Department of Psychiatry, Indianapolis, IN, USA.
3
University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacy Practice, Toledo, OH, USA.
4
University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology, Toledo, OH, USA. Electronic address: youssef.sari@utoledo.edu.

Abstract

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 β-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 β-lactam antibiotics, ampicillin, cefazolin or cefoperazone (100mg/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 β-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 β-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.

KEYWORDS:

EAAT2; alcohol intake; ampicillin; cefazolin; cefoperazone; glutamate

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