Glutamate transporters are key actors in the clearance of this excitatory neurotransmitter from the synaptic cleft in the central nervous system (CNS). So far, 5 subtypes of glutamate transporters have been described: Glutamate transporter-1 (GLT-1), Glutamate-Aspartate transporter (GLAST), Excitatory Amino Acid Carrier 1 (EAAC1) and Excitatory Amino Acid Transporters 4 and 5 (EAAT4, EAAT5). These transporters are present both on the surface of neuronal and glial cells. Nevertheless, most of the glutamate uptake is supported by GLT-1 and GLAST which are principally present on the surface of astrocytes, suggesting a key role for those cells in glutamate homeostasis in the CNS. Indeed, the persistence of elevated glutamate levels in the synaptic cleft leads to excitotoxic damages to neuronal cells. A few years ago, alternative splicings of the GLT-1 transporter have been described. These splicings lead to the generation of several transporter variants with distinct intracellular amino or carboxy-terminals or to transporter isoforms lacking internal strectches of the peptide sequence. In the literature, a variety of biochemical and pharmacological agents are known to upregulate or downregulate the activity of the GLT-1 promoter or the production of GLT-1a, the originally cloned isoform. However, little is known regarding the influence of these drugs on the alternative splicing of GLT-1. In this study, we focused our interest on the splicing of GLT-1 carboxy-terminus which generates the best characterized GLT-1a and GLT-1b isoforms. We have previously reported on an altered expression of these isoforms in a model of amyotrophic lateral sclerosis where excitotoxicity appears to play a key role. We incubated primary cultures of astrocytes during 3, 7 or 10 days in the presence of selected cytokines, growth factors or agonists of glutamate targets and evaluated the relative gene expression of these two isoforms by quantitative PCR. We have also developed a set of monoclonal antibodies that specifically recognize the two isoforms and these original tools will be used for investigating the expression profile of GLT-1 isoforms in astrocytes exposed to defined environments.