Neurophysiological and Neurochemical Mechanisms Underlying Depression Disorders and Search for New Directions of Treatment

Abstract

Depression is a severe mental pathological condition that poses a threat to life; each year, it afflicts a growing number of humans. Depression increases the risk of suicide and promotes the development of cardiovascular, metabolic, and other diseases. At present, therapy of the depressive syndrome is still insufficiently effective. Difficulties in therapeutic treatment of this syndrome are, to a considerable extent, due to the fact that it should be considered a continuum of subsyndromes based on different neurophysiological and neurochemical mechanisms. In this review, we analyze and discuss functional changes in the three main limbic structures (medial prefrontal cortex, nucl. accumbens, and basolateral nucleus of the amygdala) related to behavioral depression in animals induced by repeated introduction of glucocorticoids (GCs), action of chronic inflammation/pain, or the abstinence syndrome after withdrawal of pharmacological agents that caused drug addiction. Based on the revealed functional disorders in neuronal ensembles of the above-mentioned limbic structures, some possible pathways necessary for optimization of therapy of different variants of the depressive syndrome are proposed.