In the present study, functional activation of brain regions was measured by the induction of c-Sos and c-jun mRNA following exposure to a novel open field. Fischer 344 rats at 5 months, 14 months, and 21 months were exposed to a square open field for 20 min. Rats were then immediately sacrificed and their brains were examined for c-Sos and c-jun mRNA using in situ hybridization. Control rats were sacrificed directly from their home cage. Results showed no significant age-related changes in locomotor activity. Autoradiogram analyses showed that open-field exposure induced c-fos mRNA throughout the brain, while c-jun mRNA was induced in a few brain regions. Aged rats showed a lower elevation of c-fos mRNA in the prelimbic cortex compared to 5-month rats. In addition, grain analyses revealed age-related decreases in c-fos mRNA induction in the medial prefrontal cortex, caudate, and ventral lateral septum. These findings indicate age-related changes in the induction of c-Sos mRNA in certain brain regions following exploration of a novel environment. Copyright (C) 1996 Elsevier Science Inc.