Novel taste learning is a robust one-trial incidental learning process, dependent on functional activity of the insular (taste) cortex. In contrast to that of the cortex, the role of the hippocampus in taste learning is controversial. We set out to identify the time courses of the activation of mitogen-associated protein kinase (MAPK), transcription factor cAMP-response element-binding protein (CREB) and Akt/PKB (protein kinase B) in the insular cortex and hippocampus of rats subsequent to novel taste learning. Following taste learning, an early response (20 min) occurred at the same time in the insular cortex and the hippocampus. However, whereas MAPK was activated specifically in the insular cortex, CREB and Akt were phosphorylated in the hippocampus but not in the cortex. In addition, the immediate early gene, CCAAT/enhancer binding protein (C/EBPbeta) was induced in both the hippocampus and the insular cortex 18 h following taste learning. The results demonstrate, for the first time, correlative activation and gene expression in the hippocampus following novel taste learning. Moreover, the results suggest that different signal transduction cascades necessary for taste learning are activated in concert in different brain structures, to enable taste learning and consolidation.