Clinical evidence supports the idea of individuals that suffer stressingevents along their lives are vulnerable to developing substance use disorders(SUDs). Here, we demonstrated how exposure to chronic stressful life events canfacilitate the acquisition of cocaine self-administration (SA). We alsoattempted to prevent SA behavior by minocycline pre-treatment. Thus, rats wereexposed to chronic restraint stress (2 hs daily) during seven days. A weekafter that, animals were implanted with indwelling jugular catheters. A weekafter surgery, rats began daily 2 hs cocaine SA sessions for ten days. Four days before the onset of SA paradigm, the minocycline(30 mg/kg/12hs) or vehicle (DMSO 5%) daily treatments started, which werecarried out until the end of the SA behavior. SA consists of a fixed ratio 1schedule (FR 1) in which one response on the active lever yielded oneintravenous cocaine infusion (0.2 mg/infusion, followed by a 10 s timeoutperiod), paired with a tone and a light cue. An inactive lever was alsoavailable each session. SA criterion was defined as the first day animals obtainingmore than ten infusions of cocaine. Our results point out a facilitation of theacquisition of cocaine SA as well an augmented intake of cocaine induced bychronic stress, which was interestingly abolished by minocycline. Thesefindings constitute a starting platform to study the mechanisms underpinningthe comorbility between stress and SUDs.