Bone marrow transplantation modifies the relapse to cocaine: a possible role for peripheral IL-17A signaling

ASSIS, MARÍA AMPARO; FERRADO, ROSA; ÁVILA-ZARZA, CARMELO ANTONIO; AMBROSIO, EMILIO; DÍAZ, DAVID; WERUAGA, EDUARDO

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Introduction: Oneof the main challenges to understand drug addiction is defining the biologicalmechanisms that underlie individual differences in recidivism. Studies of thesemechanisms have mainly focused on the brain, yet we demonstrate here asignificant influence of the peripheral immune system on this phenomenon. Lewis(LEW) and Fischer 344 (F344) rats have different immunological profiles andthey display a distinct vulnerability to the reinforcing effects of cocaine,with F344 more resistant to reinstate cocaine-seeking behavior. Methods: Bone marrow from male LEW andF344 rats was transferred to male F344 rats (F344/LEW-BM and F344/F344-BM), andthese rats were trained to self-administer cocaine over 21 days. Followingextinction, these animals received a sub-threshold primer dose of cocaine toevaluate reinstatement of drug-seeking behavior. Results: F344/LEW-BM but not F344/F344-BM rats reinstatedcocaine-seeking behavior, in conjunction with changes in their peripheralimmune cell populations to a profile that corresponded to that of the LEWdonors. Cocaine treatment increased the CD4+ T-cells in F344/LEW-BMrats, and the splenic expression of Il-17A,Tgf-b, Tlr-2,Tlr-4and Il-1b wasaltered in both groups. Discussion: Wepropose that peripheral T-cells respond to cocaine, with CD4+T-cells in particular undergoing Th17 polarization and generating long-termmemory, these cells releasing mediators that trigger central mechanisms toinduce reinstatement after a second encounter. Conclusion: This immune response may explain the high rates ofrecidivism observed despite long periods of detoxification, shedding light onthe mechanisms underlying the vulnerability and resilience of specificindividuals, and opening new perspectives for personalized medicine in the treatmentof relapse.