We studied changes in the level of ceramide and sphingomyelin (SM) in the neocortex and peripheral tissues of rats after chronic (7-day-long) neurogenic stress (sessions of nociceptive stimulation in a chamber with an electrified floor) and after such stress induced against the background of course (14 days) injections of the tricyclic antidepressant imipramine. The latter agent, as is known, is a functional inhibitor of acid sphingomyelinase (aSMase). Introductions of imipramine considerably prevented manifestations of a state similar to depression (depression-like state, DLS). Suppression of motor/research activity was weakened, manifestations of emotional phenomena (acts of defecation and urination) decreased, and the latency of leaving the center of the open field became shorter. Imipramine injected into stressed animals decreased the ceramide/SM ratio and the level of ceramide in the neocortex, liver, and blood serum; the concentration of SM in the blood serum increased somewhat, as compared with the corresponding indices in rats subjected to isolated action of stress. Such changes in the levels of sphingolipids were also manifested after direct action of imipramine on isolated slices of the neocortex of stressed rats. The obtained results are indicative of the important role of the level of activity of aSMase in alterations of the ceramide/SM ratio in the neocortex of rats and in changes in the corresponding modifications of their behavior. Levels of sphingolipids in the blood serum can be the important index of the efficacy of the action of antidepressants under conditions of chronic stress and after the development of the DLS.