en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><span style="font-size:14px;"><span style="font-family:Tahoma;"><span style="line-height:2;"><b>Background:</b> Opioid use disorder (OUD) is a chronic relapsing condition characterized by high rates of stress-induced relapse even after prolonged abstinence. Converging evidence implicates neuroimmune, glutamatergic transmitters and stress-related mechanisms in relapse vulnerability. Statins exert pleiotropic anti-inflammatory and neuroprotective effects and have recently emerged as potential modulators of relapse-related processes.<br> <b>Methods:</b> Adult male Wistar rats were trained to self-administer intravenous morphine (0.5 mg/kg/infusion) for 14 days under an FR1 schedule (fixed ratio). Following acquisition, animals underwent 14 days of extinction during which they received daily intraperitoneal injections of saline or atorvastatin (1 mg/kg). Stress-induced reinstatement was triggered by intermittent foot-shock exposure on day 29. Active lever responding served as the primary index of morphine-seeking behavior.<br> <b>Results:</b> Rats acquired stable morphine self-administration across the acquisition phase. During late extinction, atorvastatin-treated animals exhibited significantly reduced active lever responding compared with saline-treated controls (p = 0.0022). Intermittent foot-shock stress robustly reinstated morphine seeking in saline-treated rats, whereas reinstatement responding was significantly attenuated in the atorvastatin group (p = 0.0022). Quantification of relapse magnitude relative to extinction baseline revealed a significantly smaller increase in active responding in atorvastatin-treated rats (&Delta; analysis, p = 0.0022). Inactive lever responding remained low across conditions.<br> <b>Conclusions:</b> Chronic atorvastatin treatment reduced morphine-seeking behavior during extinction and attenuated stress-induced reinstatement in an operant self-administration model. These findings support the potential of statins as adjunctive agents targeting relapse-related neurobiological mechanisms in OUD.</span></span></span></div> Morphine, Atorvastatin, Reinstatement, Extinction, Self-Administration 0 0 http://bcn.iums.ac.ir/browse.php?a_code=A-10-6125-3&slc_lang=en&sid=1 Niloofar Aghajani nilofaraghajani@gmail.com 13700319475328460058172 13700319475328460058172 No Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Hossein Azizi azizih@modares.ac.ir 13700319475328460058173 13700319475328460058173 No Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Saeed Semnanian ssemnan@modares.ac.ir 13700319475328460058174 13700319475328460058174 Yes Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran