Cover picture: DNA microarray analysis of the effects of brain-derived neurotrophic factor (BDNF) in the mouse nucleus accumbens. Previous work has demonstrated a role for BDNF signaling in this brain region in drug reward [Horger BA, Iyasere CA, Berhow MT, Messer CJ, Nestler EJ, Taylor JR (1999) Enhancement of locomotor activity and conditioned reward to cocaine by brain-derived neurotrophic factor. J Neurosci 19:4110-4122]. To better understand the molecular substrates for the behavioral effects of BDNF, cDNA microarray analysis was used. BDNF was infused bilaterally into the nucleus accumbens (50 ng/side) and animals were analyzed 2 d later; in other animals, BDNF was infused at a higher dose (2.5 µg/side) and animals were analyzed 2 or 4 d later. Gene expression patterns in BDNF-treated animals were compared with those in control animals, which received vehicle injections. The upper left panel shows an example of the raw array data: red spots indicate gene products that are upregulated, green spots indicate gene products that are downregulated, and yellow spots indicate gene products that are unchanged. An array can then be analyzed with scatterplots (upper right panel); most gene products are unchanged by BDNF administration (yellow), whereas some are upregulated (red) and others are downregulated (blue). BDNF regulation of thousands of gene products over time and dose can be analyzed by use of a hierarchical cluster analysis based on the Pearson correlation (lower left panel), which reveals groups of gene products that are consistently upregulated (red) or downregulated (blue) by BDNF. Highly regulated gene products can then be analyzed in isolation, for example, as shown in the lower right panel, which illustrates genes downregulated by the higher dose of BDNF. All analyses were done using Genepix and Genespring software. (By Colleen A. McClung and Eric J. Nestler, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX.) For details, see the article by Nestler in this issue (pages 8324-8327).