Minocycline prevents chronic restraint stress-induced cocaine sensitization and morphological changes of microglia within nucleus accumbens core

AVALOS, MARÍA P.; GOROSTIZA A.E; SANCHEZ MARIANELA ADELA.; GUZMAN, ANDREA S.; RIGONI, DAIANA; BOLLATI, FLAVIA A.; CANCELA, LILIANA M.

Chicago

Congreso; 2019 Neuroscience Meeting; 2019

Society for neuroscience

It is well known that individuals suffering from stress disorders are vulnerable to developing drugabuse. In animal models, studies from our lab showed that exposure to restraint stress engenderslong-lasting neuroadaptations on glutamatergic system within Nucleus Accumbens (NA) whichenables sensitized response to cocaine (Esparza et al., 2012, García-Keller et al., 2013) andfacilitation of cocaine self-administration (García-Keller et al 2016). On the other hand, ourprevious findings evidenced a role of glutamate in enduring psychostimulant-induced sensitizationat 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 stressinduced cocaine sensitization. The aim of this study was to evaluate the effect of minocycline,apotent inhibitor of microglia activation, on chronic restraint stress-induced cocaine sensitizationand morphological changes of microglia within NA core. Thus, Sprague Dawley rats were exposedto restraint stress 2 h daily for a week. From day 16 to day 21 after the first stress session, allanimals 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 orderto examine fluorescence intensity and the morphology of microglia, immunofluorescence bylabeling iba-1 was performed. Our results showed that minocycline was able to prevent chronicstress-induced cocaine sensitization suggesting that microglia play a key role in this phenomenon.Interestingly, stress induced hyper-ramification of microglia and enhancement of iba-1fluorescence intensity within Na core. Likewise, minocycline prevented those morphologicalchanges of microglia and restored the expression of iba-1. Accordingly, we propose that microgliacould contribute to the development of pathological neuroadaptations within NA core followingchronic restraint stress to trigger cocaine sensitization.These results strongly prompt to think thatminocycline 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 topromote addiction-related disorders.