The normal function of the mammalian brain is regulated by complex networks of interactions between cells and molecules, which are to a considerable extent dependent on mechanisms of transcriptional regulation. Disruption of such interactions by neurotoxic stimuli may lead to severe forms of dementia and to other neuropsychiatric disorders. Therefore, critical insight into mechanisms of neuronal dysfunction may be obtained by examining global patterns of gene expression in mammalian models of neurotoxicity. In this regard, the combined use of rat neuronal cultures and serial analysis of gene expression (SAGE) can be viewed as a general platform to enable the search for molecular targets involved in neurotoxic processes. Here, we discuss potential advantages of this approach, highlighting the need for generation of robust SAGE libraries from rat neuronal cultures. The availability and current limitations of bioinformatics tools for SAGE data derived from rat samples is also discussed.