Activin A is increased in the nucleus accumbens following a cocaine binge.

Drug addiction is a long-lasting disease characterized by compulsive drug intake mediated in part by neuronal and biological adaptations in key brain areas, such as the nucleus accumbens (NAc). While we previously demonstrated involvement of the activin 2a receptor in drug taking, the role of its ligand, activin A, in cocaine relapse is unknown. Activin A levels in the NAc were assessed via ELISA and immunohistochemistry (in neurons, astrocytes, and microglia) following a cocaine binge paradigm. Cocaine exposure significantly increased the levels of activin A in the NAc of animals that had self-administered cocaine prior to the 14-day withdrawal compared with levels in saline controls. This was accompanied by an increase in the proportion of IBA1 microglia in the NAc that were immunopositive for activin A. In contrast, the proportions of NeuN neurons and GFAP astrocytes that were immunopositive for activin A remained unaltered. In conclusion, these data suggest that increased secretion of activin A, particularly from microglia, in the NAc represents a novel potential target for the treatment of cocaine relapse.