Effect of the analgesics dipyrone, tramadol, and meloxicam on the behavior of laboratory rats

A B S T R A C T Awareness about the ethical use of laboratory animals has increased over recent decades alongside the development of strict guidelines and legislation concerning the welfare of animals in scientific research. Although minimization of animal suffering during experimentation is of paramount importance, it is sometimes neglected because of the presumed interference of analgesics on behavioral patterns. For this reason, comprehensive research with multiple pharmacological agents is vital if analgesics are to be in-cluded in experimental procedures. In this context, we aimed to evaluate the effects of the analgesics dipyrone (DIP), tramadol (TRA), meloxicam (MEL), and combinations thereof on the behavioral parame-ters of naive laboratory rats. Forty-eight SPF male Wistar-Han rats were divided randomly into 6 equal groups (n = 8 per group) and treated by intraperitoneal injection with DI (178 mg/kg), TRA (17.8 mg/kg), MEL (1.5 mg/kg), DIP + TRA (178 + 17.8 mg/kg), MEL + TRA (1.5 + 17.8 mg/kg) or saline (SAL; control). The behavior of the treated animals was assessed 30 minutes after injection of analgesic by sequential sub-mission to Open Field, Elevated Plus Maze, and Grooming Transfer tests. Treatment with DIP + TRA pro-voked the most significant alterations in rat behavior by reducing locomotion, rearing, and grooming. Although treatment with DI alone diminished exploratory behavior, the effect on grooming was not re-markable, thereby suggesting that DI has a suppressive motor effect, possibly caused by its action on the endocannabinoid system, which is potentiated by TRA. In the Open Field tests, the grooming behavior of all TRA-treated animals was reduced while treatment with MEL increased locomotion. Given that analge-sia is an ethical duty, the experimental design should always consider the behavioral effects of the drugs themselves.(c) 2022 Elsevier Inc. All rights reserved.