Background and Aims: The emergence of tolerance to morphine presents an obstacle in 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 are not yet fully elucidated. This study aimed to assay the effects of SUV on tolerance to morphine and its impact on the expression of DRD2 and NR1 genes in the mouse brain.
Materials and Methods: A total of 28 male mice were randomly allocated into 4 groups. Morphine tolerance was induced through repeated morphine injections. SUV (90 mg/kg), clonidine (0.1 mg/kg), and normal saline were administered (ip) 30 minutes before morphine injection. Tail-flick and open field tests were performed on day 4. The expression levels of the DRD2 and NR1 genes were quantitatively assessed through RT-PCR analysis.
Results: 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 ± 0.8659, P < 0.05) but did not alter the expression of the NR1 gene (P > 0.05).
Conclusion: This finding indicated that SUV reduced tolerance to morphine. SUV administration decreased relative expression of the DRD2 gene but had no effect on NR1 gene expression. To our knowledge, these findings provide first evidence that SUV may attenuate morphine tolerance predominantly through modulation of the dopaminergic system.