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

Chicago

Conferencia; Neuroscience 2019; 2019

SfN

It is well known in the field of addiction that exposure to stressful events is one of the most significant risk factors to the development of drug abuse. Thereby, studies from our lab showed that exposure to restraint stress engenders long-lasting neuroadaptations on glutamatergicsystem in 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). Nevertheless, the neurobiological mechanisms underpinning this comorbidity have not been fully elucidated yet.On the other hand, our previous findings evidenced a role of glutamate in enduring psychostimulant-induced sensitization phenomenon at the immune level in a parallel way to that occurring in the limbic system (Assís et al., 2009, 2011). However, there is currently no description so far of which is the role played by microglia in psychostimulant-induced sensitization phenomenon.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. Sprague Dawley rats were exposed to restraint stress 2 h daily for a week. From day 16 after the first stress session, all animals were treated with minocycline (30 mg/Kg/12 h) or vehicle (DMSO 5%/12 h) for 5 days. On day 21, locomotor activity was measured following saline or cocaine challenge (15 mg/Kg) and rats were transcardially perfused with 4% PFA solution to perform immunofluorescence by labeling iba-1 (microglia marker) in order to examine fluorescence intensity and the morphology of microglia in NA core. Our results pointed out 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. Likewise, minocycline prevented morphologicalchanges of microglia and restored the expression of iba-1. Accordingly, we propose that microglia could contribute to the development of pathological neuroadaptations 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