The tetracycline doxycycline (Dox) has been reported to have neuroprotective effects unrelated to its antibiotic activity. Previous evidence show a beneficial effect of Dox in rodent models of Parkinson disease by 6-OHDA lesion (1-2). Our present aim was to determine whether Dox could rescue behavioral and biochemical phenotypes related in the htau mouse model of tauopathy. Htau mice develop a combination of phenotypes including cognitive decline, motor coordination and olfactory deficits , related to the pathological tau accumulation in the prefrontal cortex and the striatum (3). Phenotypic onset in this model starts at 6 months old (4). In this study, htau mice were treated chronically with doxycycline in their diet from 6 months-old onwards. Behavioral phenotypes were analyzed at 6 and 12 months-old to determine time course of behavioral deficits. At the end of treatment, biochemical studies were performed to determine phospho-tau levels and inflammatory markers. The Dox treatment improved motor coordination and olfactory deficits in htau mice, compared with the placebo group. We observed a parcial rescue in IL-10, GFAP and phospho-tau contents specifically in striata of Dox treated htau mice. Further research is under way to investigate the molecular pathways leading to the beneficial effect of Dox over tauopathy phenotypes in this model.