Chronic continuous perfusion of the hibernation triggering opioid DADLE did not cause any major physiological alterations in rats

Abstract

[D-Ala(2), D-Leu(5)] enkephalin (DADLE), a delta opioid receptor agonist, can induce mammalian hibernation and has hibernation-like effects in non-hibernating species. It has also been demonstrated that DADLE has protective efficacy on various tissues such as nervous, cardiac, and hepatic tissues. Despite substantial research conducted in the last decade about the tissue protective efficacy of DADLE, detailed underlying mechanisms have not been fully elucidated. In the present study we investigated in a rat model whether continuous perfusion of DADLE can induce potentially tissue protective alterations in physiological parameters. In the study 48 young male Wistar rats were used. They were divided into control and experimental groups, each group consisting of 24 animals. DADLE was perfused to experimental group rats continuously for 28 days using subcutaneously implanted osmotic mini-pumps. We investigated its effects on body temperature, antioxidant protection [total antioxidant capacity (TAC), ascorbic acid (AA), and malondialdehyde (MDA) levels], white blood cell (WBC) count, and coagulation parameters [activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT)]. While thrombin time was significantly lengthened in the DADLE treated group, there were no statistically significant differences in the other investigated parameters between the experimental group and the control group.