CONICET | Buscador de Institutos y Recursos Humanos

Minocycline prevents chronic restraint stress-induced cocaine sensitization and morphological changes of microglia within nucleus accumbens coreAvalos M.P., Gorostiza A.E., Sanchez M.A., Guzman A.S., Rigoni D., Bollati F.A. and Cancela L.M.IFEC-CONICET.Department of Pharmacology, School of Chemical Sciences, National University of Cordoba, Argentina.It is well known that individuals suffering from stress disorders are vulnerable to developing drug abuse. In animal models, studies from our lab showed that exposure to restraint stress engenders long-lasting neuroadaptations on glutamatergic system within Nucleus Accumbens (NA) which enables sensitized response to cocaine (Esparza et al., 2012, García-Keller et al., 2013) and facilitation of cocaine self-administration (García-Keller et al 2016). On the other hand, our previous findings evidenced a role of glutamate in enduring psychostimulant-induced sensitization at the immune level in a parallel way to that occurring in the limbic system (Assis et al., 2009, 2011). However, there is no description so far of which is the role played by microglia in stress-induced cocaine sensitization. The aim of this study was to evaluate the effect of minocycline,a potent inhibitor of microglia activation, on chronic restraint stress-induced cocaine sensitization and morphological changes of microglia within NA core. Thus, Sprague Dawley rats were exposed to restraint stress 2 h daily for a week. From day 16 to day 21 after the first stress session, all animals were treated with minocycline (30 mg/Kg/12 h) or vehicle (DMSO 5%/12 h). On day 21, locomotor activity was measured following saline or cocaine challenge (15 mg/Kg). Then, in order to examine fluorescence intensity and the morphology of microglia, immunofluorescence by labeling iba-1 was performed. Our results showed that minocycline was able to prevent chronic stress-induced cocaine sensitization suggesting that microglia play a key role in this phenomenon. Interestingly, stress induced hyper-ramification of microglia and enhancement of iba-1 fluorescence intensity within Na core. Likewise, minocycline prevented those morphological changes of microglia and restored the expression of iba-1. Accordingly, we propose that microglia could contribute to the development of pathological neuroadaptations within NA core following chronic restraint stress to trigger cocaine sensitization.These results strongly prompt to think that minocycline might be considered as a promising therapeutic agent in preventing this comorbidity. Next findings will attempt to deepen the study of these chronic restraint stress-induced changes to promote addiction-related disorders.