en Pharmacology Pharmacology مقاله پژوهشی Original Research Article <p style="text-align: justify;"><span style="font-size:16px;"><span style="font-family:Times New Roman;"><b><span style="background:#2d7f8f"><span style="color:white">Background & Objective:</span></span><b> </b></b><span style="color:black">The emergence of tolerance to morphine presents an obstacle to its therapeutic use. Suvorexant (SUV) has demonstrated efficacy in mitigating the addictive properties of drugs. Nevertheless, the exact pathways through which SUV exerts its influence remain poorly elucidated. This study investigated whether SUV influences the development of morphine tolerance and examined its impact on DRD2 and NR1 gene expression in the mouse brain.</span><br> <b><span style="background:#2d7f8f"><span style="color:white"><span style="letter-spacing:-.1pt">&nbsp;Materials & Methods:</span></span></span></b> <span style="color:black"><span style="letter-spacing:-.1pt">The study involved 28 male mice, which were randomly allocated into four groups. Morphine tolerance was induced through repeated morphine injections. Clonidine (0.1 mg/kg), SUV (90 mg/kg), and normal saline were administered (<i>ip</i>) 30 minutes before morphine injection. Tail-flick and open field tests were performed on day 4. Quantitative assessment of DRD2 and NR1 gene expression was performed using RT-PCR.</span></span><br> <b><span lang="EN-IN"><span style="background:#2d7f8f"><span style="color:white">Results: </span></span></span>&nbsp;</b><span style="color:black"><span style="letter-spacing:-.1pt">Repeated morphine injections led to a notable decrease (P < 0.001) in reaction time. Both SUV (P<0.05) and clonidine (P<0.001) indicated a significant reduction in the progression of morphine tolerance. SUV significantly reduced the elevated relative expression of the DRD2 gene (fold change = 1.628 &plusmn; 0.8659,<i> </i>P < 0.05) but did not alter the expression of the NR1 gene (P > 0.05)</span></span><span dir="RTL" lang="FA"><span style="color:black"><span style="letter-spacing:-.1pt">.</span></span></span><span style="color:black"><span style="letter-spacing:-.1pt"></span></span><br> <b><span style="background:#2d7f8f"><span style="color:white">Conclusion: </span></span>&nbsp;</b><span style="color:black">This finding indicated that SUV reduced tolerance to morphine. SUV administration decreased the relative expression of the DRD2 gene but did not affect NR1 gene expression. To our knowledge, these findings provide the first evidence that SUV attenuates morphine tolerance predominantly by modulating the dopaminergic system.</span></span></span></p> Orexin, Suvorexant, Morphine, Drug Tolerance, Dopamine Receptor D2 337 346 http://journal.zums.ac.ir/browse.php?a_code=A-10-7273-1&slc_lang=en&sid=1 Peyman Esmaili-Shahzade-Ali-Akbari peyman.esmaely@gmail.com 5200319475328460087471 5200319475328460087471 No Clinical Research Development Unit of Shahid Beheshti Hospital, Kashan University of Medical Sciences, Kashan, Iran Amir Ghaderi gaderiam@yahoo.com 5200319475328460087472 5200319475328460087472 Yes Social Determinants of Health (SDH) Research Center, Kashan University of Medical Sciences, Kashan, Iran Behrang Alani behrangha@yahoo.com 5200319475328460087473 5200319475328460087473 No Autoimmune Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran Elahe Seyed Hosseini elaheir.1987@gmail.com 5200319475328460087474 5200319475328460087474 No Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran Freshteh Haerifar peyman.esmaely@chmail.ir 5200319475328460087475 5200319475328460087475 No Clinical Research Development Unit of Shahid Beheshti Hospital, Kashan University of Medical Sciences, Kashan, Iran