Oral glutamate intake reduces acute and chronic effects of ethanol in rodents

Araya Supawat,Supawadee Srisuwan,Jintana Sattayasai

doi:10.4314/tjpr.v15i7.20

Abstract

Purpose: To assess the effects of oral glutamate intake on acute motor effects and chronic intake of ethanol in rodents. Methods : The acute effects of ethanol on motor function were studied in ICR mice by giving 2 or 6 g/kg of ethanol 2 h after distilled water or 2.5 g/kg glutamate per os. Thirty minutes after ethanol treatment, behavioral assays, including rotarod tests and foot print analysis were monitored. In chronic ethanol treatment, male Wistar rats were trained to consume ethanol-sucrose solution during a 2-h period daily, starting with 2 % ethanol/10 % sucrose and gradually increasing to 10 % ethanol/5 % sucrose solution over 56 days. After training session, the drug treatment phase was done for 10 days. The animals were force-fed 50 mg/kg/day topiramate or 2.5 g/kg/day glutamate 2 h before ethanol treatment sessions. Each day, ethanol intake, water intake, food intake and body weight were recorded. Results : Mice that received 2 or 6 g/kg of ethanol orally, showed a significant reduction in time on the rod in the rotarod test and a significant increase in both forelimb and hindlimb stride lengths when compared to control. Oral treatment with 2.5 g/kg of glutamate reversed the acute motor effects of ethanol. In chronic ethanol treatment, the intake of 10 % ethanol/5 % sucrose, accessible for 2 h, was significantly decreased in rats treated with either topiramate or glutamate. Conclusion : These results provide evidence that oral glutamate administration help to reduce the acute motor effects of ethanol in mice and ethanol intake in the chronic ethanol drinking rats. Keywords : Ethanol, Glutamate, Motor functions, Ethanol intake, Rodents

Highlights

Glutamate, the principal excitatory amino acid neurotransmitter present in the mammalian brain, is one of the neurotransmitters responsible for neuronal effects of ethanol in both acute and chronic alcohol consumption
Time on rods of mice that received glutamate with either 2 or 6 g/kg of ethanol were comparable to the control which suggested that glutamate could completely reverse the effects of ethanol
Mice that received 2.5 g/kg glutamate could reverse the effects of 2 g/kg, but not 6 g/kg, of ethanol on forelimb stride length (FSL) and hindlimb stride length (HSL) to the control length

Summary

Introduction

The principal excitatory amino acid neurotransmitter present in the mammalian brain, is one of the neurotransmitters responsible for neuronal effects of ethanol in both acute and chronic alcohol consumption. All glutamate receptors, including N-methyl-D-aspartate (NMDA) and L-alphaamino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ionotropic (AMPA) receptors are inhibited [1]. Together with increased inhibitory neurotransmission through gamma-aminobutyric acid (GABA), acute alcohol exposure leads to a sedated state and impaired motor coordination in drinkers [1,2]. Several studies have focused on the investigation of glutamatergic agents in maintaining glutamate homeostasis, modifying alcohol’s effects, and reducing alcohol intake [7,8]. Topiramate, an anticonvulsant, that inhibits glutamate release and blocks AMPA/kainate receptors, can be used in the treatment of alcohol dependence [11]

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