NeuropharmacologyMay 24, 2015

Ceftriaxone reduces alcohol drinking and restores glutamate balance by normalizing its transporter in the reward system of male alcohol-preferring rats

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

Ceftriaxone treatment significantly reduced ethanol intake in male P rats.

Chronic ethanol drinking increased extracellular glutamate levels in the nucleus accumbens of saline-treated rats compared to water controls.
Ceftriaxone treatment blocked the increase in extracellular glutamate caused by ethanol intake.
The blockade of glutamate transporter 1 (GLT-1) with dihydrokainic acid reversed ceftriaxone's effects on glutamate levels.
GLT-1 protein levels were decreased in rats exposed to ethanol, but ceftriaxone treatment reversed this deficit.
Ceftriaxone also enhanced glutamine synthetase activity in the nucleus accumbens compared to saline-treated rats that consumed ethanol.

Simplified

Alteration of glutamatergic-neurotransmission is a hallmark of alcohol dependence. We have previously reported that chronic ethanol-drinking downregulated glutamate transporter 1 (GLT-1) in nucleus accumbens (NAc) in male P rats in a manner that was reversed by ceftriaxone treatment. However, the effect of ceftriaxone on extracellular glutamate concentrations in NAc after chronic ethanol-drinking has not yet been studied. In the present study, male P rats were treated with ceftriaxone (100 mg/kg/day, i.p.) for five consecutive days following five-weeks of free choice ethanol (15% and 30%) drinking. In vivo microdialysis was performed to measure the extracellular glutamate concentrations in NAc and the effect of blockade of GLT-1 with dihydrokainic acid (DHK) on extracellular glutamate in NAc of ceftriaxone-treated rats was determined. Ceftriaxone treatment attenuated ethanol intake as well as ethanol preference. Extracellular glutamate was significantly higher in NAc after five-weeks of ethanol drinking in saline-treated compared to water control rats. Ceftriaxone treatment blocked the increase extracellular glutamate produced by ethanol intake. Blockade of GLT-1 by DHK reversed the effects of ceftriaxone on glutamate and implicated the role of GLT-1 in the normalization of extracellular glutamate by ceftriaxone. In addition, GLT-1 protein was decreased in ethanol exposed animals and ceftriaxone treatment reversed this deficit. Ceftriaxone treatment also increased glutamine synthetase activity in NAc but not in PFC as compared to ethanol drinking saline-treated rats. Our present study demonstrates that ceftriaxone treatment prevents ethanol drinking in part through normalization of extracellular glutamate concentrations in NAc of male P rats via GLT-1.

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Ceftriaxone reduces alcohol drinking and restores glutamate balance by normalizing its transporter in the reward system of male alcohol-preferring rats

Abstract

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