CONICET | Buscador de Institutos y Recursos Humanos

One of the main challenges to understand drug addiction is to define the mechanisms underlying individual predisposition to recidivism. Those and other processes related with addiction have been almost exclusively studied regarding at brain functioning. However, some phenomena of drug reinstatement cannot be solely explained by neuronal mechanisms. In this sense, Lewis (LEW) and Fischer 344 (F344) rats show differential vulnerability to the reinforcing effects of several drugs of abuse, including cocaine, the F344 being more resistant to reinstate the drug-seeking behaviour than LEW rats. Both strains have also different rates of peripheral lymphocytes, and it is plausible to think that these dissimilarities could participate in their differential behavioural responses. Here we have transferred immune cells from LEW to F344 rats by bone marrow ablation and transplantation. After 3 weeks of cocaine self-administration, extinction, and priming, the chimeric F344/LEW-BM rats reinstated cocaine-seeking behavior -unlike their controls- and presented a pattern of peripheral immune cells similar to LEW donors. Remarkably, few transplant-derived elements (mainly T-cells, but also microglia) were detected into the recipient?s brain. We did not detect any preference for integration into addiction-related areas, nor a specific change in the distribution compared to standard situations. Conversely, cocaine treatment increased CD4+ T-cells (related to long-term immune memories) in F344/LEW-BM rats, also changing the splenic expression of immune-related genes (i.e. D5 receptor, TLR-4 and TLR-2). Our results demonstrate a significant role of the peripheral immune system in drug reinstatement and open new perspectives in the treatment of relapse.