Minocycline prevents cross-sensitization between stress and cocaine and the increased expression levels of proinflammatory cytokines induced by chronic restraint stress

Buenos Aires

Congreso; 2° Congreso FALAN; 2016

Scientific evidence including ours,supports the idea of both stress and drugs of abuse share commonneurobiological substrates.Even more, clinical evidence proved that individuals who suffer stressingeventsalong their lives are vulnerable to developing substance use disorders.Moreover, our previous findingsshowed along-lasting psychostimulant-induced sensitization phenomenon at the immunelevel in a parallelway to that occurring in the limbicsystem (Assís et al., 2006, 2009, 2011). However, the mechanismsunderpinning the comorbiditybetween stress and substance use disorders have not been elucidated yetandthere is no description so far of which is the role played by the immune systemin sensitizationphenomenon. Here, we study the participation ofproinflammatory cytokines on cocaine cross-sensitizationinduced by stress. Thus, male rats were exposed to chronic restraint stressdaily during 7 days. 5 days beforethe measurement of locomotor activity (LA),animals were treated with minocycline (30 mg/kg i.p./12hs) orvehicle (DMSO 5%)daily during 5 days. During LA we tested psycomotor response to salineinjection followedby a cocaine challenge (15 mg/kg i.p.) on day 21 after defirst stress session. TNF-α and IL-6 mRNAexpression levels were quantified byqPCR in nucleus accumbens. Chronic stress induced cocaine cross-sensitizationand increased production of TNF-α and IL-6 which were preventedby minocycline. Theseresults could be key to a better understanding of the roleof proinflammatory cytokines in the immunologicalsignaling system in thevulnerability to develop drug addiction induced by stress and it may provide anewtherapeutic target.