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

AVALOS MARIA PAULA; BOLLATI FLAVIA; RIGONI DAIANA; GUZMAN ANDREA SUSANA; PERALTA-RAMOS JAVIER; IRIBARREN PABLO; CANCELA LILIANA M

Buenos Aires

Congreso; 2nd Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN).; 2016

Scientific evidence including ours, supports the idea of both stress and drugs of abuse share common neurobiological substrates. Even more, clinical evidence proved that individuals who suffer stressing events along their lives are vulnerable to developing substance use disorders. Moreover, our previous findings showed a long-lasting psychostimulant-induced sensitization phenomenon at the immune level in a parallel way to that occurring in the limbic system (Assís et al., 2006, 2009, 2011). However, the mechanisms underpinning the comorbidity between stress and substance use disorders have not been elucidated yet and there is no description so far of which is the role played by the immune system in sensitization phenomenon. Here, we study the participation of proinflammatory cytokines on cocaine cross-sensitization induced by stress. Thus, male rats were exposed to chronic restraint stress daily during 7 days. 5 days before the measurement of locomotor activity (LA), animals were treated with minocycline (30 mg/kg i.p./12hs) or vehicle (DMSO 5%) daily during 5 days. During LA we tested psycomotor response to saline injection followed by a cocaine challenge (15 mg/kg i.p.) on day 21 after de first stress session. TNF-α and IL-6 mRNA expression levels were quantified by qPCR in nucleus accumbens. Chronic stress induced cocaine cross-sensitization and increased production of TNF-α and IL-6 which were prevented by minocycline. These results could be key to a better understanding of the role of proinflammatory cytokines in the immunological signaling system in the vulnerability to develop drug addiction induced by stress and it may provide a new therapeutic target.