Drug addiction poses a significant public health challenge, impacting individuals and societies at large. While substantial progress has been made in understanding the neurobiological underpinnings of addiction, certain aspects remain unresolved. Satb2 is a DNA-binding protein involved in gene expression regulation through chromatin remodelling. We propose that it can emerge as a potential player in addiction mechanisms. A Satb2 conditional mutant (cKo) (Satb2 flox/flox::Camk2a-cre) that was generated showed impairment in long-term memory and an absence of this gene in the Cortex and CA1 region of the hippocampus from the third post-natal week on. The present study aims to characterise this mouse model on the behavioural and molecular levels. Using the Conditional Place Preference model of addiction, we compared reinstatement to cocaine-induced by cocaine priming, as well as stress (Forced swim test - FST), between Satb2 cKO and floxed control mice. These mice did not differ in the extinction or the reinstatement to cocaine, nevertheless, we observed a significant increase in immobility time in the FST between the two groups of mice. At the molecular level, we intend to identify the brain regions where Satb2 is expressed in mice. Moreover, activated Satb2 in different brain regions in mice that extinguished and did not extinguish cocaine preference, will be assessed. These efforts will provide significant insights into the molecular mechanisms behind cocaine addiction; furthermore, they have the opportunity to guide the development of efficacious drugs that target relapse in addition.Research in collaboration with the Institute for Neuroscience (MUI).