The effect of restraint stress on c-jun mRNA expression in the hippocampal formation was investigated by in situ hybridization, dot blot and northern blot. c-jun mRNA expression increased after 60 min of forced restraint in the dentate gyrus, CA1 and CA3 regions of the hippocampal formation. The effect in the dentate gyrus was attenuated by pre-stress i.c.v. injection of the anxiolytic benzodiazepine midazolam (20 nmol/2 microl) or the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-7-phosphonoheptanoic acid (AP-7, 5 nmol/2 microl), but not by the 5-HT1A agonist, (+/-) 8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 20 nmol/2 microl). These results suggest that the hippocampal formation is activated during restraint stress, and that this activation is modulated by benzodiazepine/GABA-A or NMDA receptors.