The present study examines the influence of electroconvulsive seizure (ECS), as well as several antidepressant drug treatments, on the induction of c-fos mRNA in response to acute restraint stress. Acute (45-minute) restraint stress resulted in five- to sixfold elevation of c-fos mRNA levels in rat frontal cortex. Chronic administration of ECS significantly decreased the induction of c-fos mRNA levels in response to acute restraint stress, and this effect was observed after chronic (6 to 9 days) but not acute (1 or 3 days) of ECS treatment. In addition, c-fos induction in response to acute restraint stress was down-regulated by chronic, but not acute, administration of tranylcypromine or imipramine, two drugs that nonselectively increase synaptic levels of norepinephrine and serotonin by inhibition of monoamine oxidase or neurotransmitter reuptake, respectively. Moreover, chronic administration of desipramine or sertraline, selective re-uptake inhibitors of norepinephrine, or serotonin, respectively, also significantly down-regulated the induction of c-fos mRNA in response to restraint stress. Chronic administration of ECS, tranylcypromine, or imipramine also decreased stressed-induced levels of NGFI-A mRNA, another immediate early gene transcription factor, whereas levels of c-jun mRNA were not influenced by either stress or antidepressant treatments. The results demonstrate that chronic, but not acute, administration of ECS and several different classes of antidepressant drugs down-regulates stress-induced levels of c-fos mRNA, suggesting that this effect may be a common, postreceptor action of antidepressant treatments.