1. The effects of restraint stress on c-fos mRNA expression in the dentate gyrus were investigated by in situ hybridization. 2. Confirming previous findings, c-fos mRNA expression increased after 30 min of forced restraint. 3. This effect was attenuated by a previous i.c.v. injection of the anxiolytic benzodiazepine midazolam (20 nmol/2 microliters) or the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-7-phosphonoheptanoic acid (AP-7; 5 nmol/2 microliters). 4. These results suggest that the dentate gyrus is activated during restraint stress and that this activation may be modulated by benzodiazepine gamma-aminobutyric acidA (GABAA) or NMDA receptors.