The Midbrain Dopaminergic System in Behavioral Models of Depression

The dopaminergic system of the midbrain is involved in the pathogenesis of depression but the nature of its involvement is illusive. The review is focused on behavioral models of depression demonstrating changes in the activity of the dopaminergic system during the development of depressive-like behavior. Such changes in various target structures of dopaminergic neurons, as a rule, are multidirectional and it is still hard to systematize them. Some of the demonstrated changes indicate the role of synaptic and/or homeostatic plasticity. At the same time, interpreting the results obtained in behavioral models is associated with a large number of limitations, some of which are discussed in the presented work. The most significant, in our opinion, is the need to take into account the various strategies implemented by animals in response to stress. One of the key characteristics of stressful effects that determine their impact on the organism is the ability of an individual to control these effects; it is in this regard that the results of the most valid behavioral model - the social defeat model—are ambiguous. At the same time, these problems allow us to outline important directions for further research: studying the participation of dopamine-dependent mechanisms of instrumental learning in the formation of depressive-like behavior. The steps taken in this direction already allow researchers to make therapeutically significant generalizations. Such a discourse allows us to consider depression as an experience, as was done with respect to addiction. The high comorbidity of depression and addiction, the great similarity of the depressive syndrome and hyperkatifeia in addiction, as well as the shared neurophysiological substrate of both disorders, lead us to hypothesize that there are similar mechanisms of pathological changes at critical stages in the development of these disorders.