Introduction Attention-deficit/hyperactivity disorder (ADHD) is a common neurological disorder of the adolescent age characterized by hyperactivity, impulsivity and inattention. However, etiopathogenesis of this disorder remains controversial, partly due to the lack of relevant animal model. Nevertheless, given its role in the regulation of high-level executive functions, consensus interpretation considers a dysregulated Prefrontal Cortex (PFC) is critical in the emergence of ADHD. With profound maturation processes during developmental period from childhood to early puberty, including synaptic pruning and myelination during adolescence, the PFC is a brain structure vulnerable to environmental insults. Considering the dearth in studies evaluating the deleterious impact of stress during adolescence, in particular its consequences on hypofrontality, we endeavor to develop a preclinical model of ADHD by subjecting adolescent rats to chronic mild stress. Methods Adolescent male rats were subjected to chronic unpredictable mild stress [1] for 3 consecutive weeks starting from the post-weaning phase (21 days). The stress procedure was a combination of a series of unpleasant situations, repeated over the week, composed of inclined cage (30 degrees), isolation followed by overnight pairing with a non-cage mate, wet bedding, food restriction and elevated platform (for 30 min only). The stress procedure was administered pseudo randomly with exposure to different stressors twice a day; for 2 hours in the morning and 2 hours in the afternoon. The control rats were handled daily but were not subjected to any stress. Then the rats were exposed to a series of behavioral experiments. A set of rats were sacrificed immediately after the stress procedure and the prelimbic pyramidal neurons were tested electrophysiologically. Results In line with the procedure they were exposed to, rats exhibited an attenuated corticosterone response to acute stress (p=0.0109) compared to control mates. They spent a significantly higher time exploring the open arms of the elevated plus maze (p Conclusion We have successfully developed a preclinical model of ADHD after subjecting adolescent rats to chronic mild stress. This model shows the phenotypic hallmarks of ADHD, namely, disinhibition, hyperactivity, impulsivity and inattention that correlates with decreased excitability of pyramidal neurons of the prelimbic cortex. Future studies will evaluate pharmacological effects of drugs on the stress rats.