The paper presents a summary of results considering cholinergic hypothesis on the central processes of human stress response and depression caused by chronic social stress. These studies include both the work of clinicians, who are examining pathogenesis of depression, and experiments with rodents. The authors also consider the history of stress response discovery in humans and vertebrates. The paper analyses the results of early studies (1980s-1990s), which led to the hypothesis on the key role of brain cholinergic system in nonspecific stress response of the whole multicellular organism of humans and rodents. Special attention is paid to the latest ideas on acetylcholine as the most powerful neuromodulator in the brain. Acetylcholine is said to transmit large volumes of information. The authors conducted the summary of experimental and clinical studies showing that the primary reaction of humans and rodents under stress is manifested in the activation of brain cholinergic transmission, but not in subsequent changes in serotonergic system functioning. The paper analyses numerous studies, the result of which confirmed the cholinergic hypothesis on stress and depression. These facts are as follows: firstly, the increase in the acetylcholine level in the brain or in the hippocampus (physostigmine injection) causes similar changes in the behavior and physiological state of rodents under stress; secondly, single-time stress increases the acetylcholine level in several areas of the brain, thus, correlating to adaptive changes in behavior; thirdly, chronic stress that causes disturbances in rodent behavior, which are similar to depression, is accompanied by an increase of the acetylcholine level in the brain. In general, the authors come to the conclusion that ideas on the key role of cholinergic system in stress response can serve as a scientific basis for further research on the depression mechanisms both clinically and experimentally
Keywords: stress, depression, acetylcholine, neuromodulator, behavior.
