Is It Possible to Shift from Down to Top Rank? A Focus on the Mesolimbic Dopaminergic System and Cocaine Abuse

Abstract

Impaired social behavior is a common feature of many psychiatric disorders, in particular with substance abuse disorders. Switching the preference of the substance-dependent individual toward social interaction activities remains one of the major challenges in drug dependence therapy. However, social interactions yield to the emergence of social ranking. In this review, we provide an overview of the studies that examined how social status can influence the dopaminergic mesolimbic system and how drug-seeking behavior is affected. Generally, social dominance is associated with an increase in dopamine D2/3 receptor binding in the striatum and a reduced behavioral response to drugs of abuse. However, it is not clear whether higher D2 receptor availability is a result of increased D2 receptor density and/or reduced dopamine release in the striatum. Here, we discuss the possibility of a potential shift from down to top rank via manipulation of the mesolimbic system. Identifying the neurobiology underlying a potential rank switch to a resilient phenotype is of particular interest in order to promote a positive coping behavior toward long-term abstinence from drugs of abuse and a protection against relapse to drugs. Such a shift may contribute to a more successful therapeutic approach to cocaine addiction.

Dopamine D2 receptors in the dorsomedial prefrontal cortex modulate social hierarchy in male mice

“…DA functions through two groups of G-protein-coupled receptors, DA receptors 1 and 2 (D1Rs and D2Rs), which exert divergent functions due to different intracellular signaling pathways and properties ( Li et al 2020 ; Kourosh-Arami et al 2022 ). Numerous studies investigated the contributions of DA receptors in social dominance but with inconclusive results depending on the intervening measures, related brain structures, species, or many other unknown reasons ( Ghosal et al 2019 ; Amaral et al 2021 ). D1Rs and D2Rs are abundantly expressed in the mPFC, which play critical but distinct roles in social information processing in rodents ( Shinohara et al 2018 ; Xing et al 2021 ).…”