Abstract text (incl. figure legends and references)

Objective: The development of novel targets within brain research often requires surgical procedures in rodents, and opioid analgesia is frequently needed postoperatively. Buprenorphine is a partial agonist of the μ-opioid receptors and has a strong analgesic effect when acting on the central nervous system. A long-acting buprenorphine formulation would be highly beneficial to avoid frequent dosing of postoperative animals. However, buprenorphine depot formulations developed for animal use are not available in Europe. The purpose of the present study was therefore to evaluate the effect on rats of a long-acting subcutaneous (s.c) depot injection with buprenorphine available for humans (Buvidal).

Methods: Spraque Dawley rats were used. The depot formulation (Buvidal, 1.5mg/kg s.c, n=24) was evaluated and compared to a short-acting buprenorphine formulation commonly used in laboratory rodents (Temgesic, 0.1 mg/kg s.c, n=18) and negative control (s.c saline, n=24). The analgesic effect was assessed using the von Frey pressure test on the plantar surface of the right hind paw, allowing analgesic efficacy to be evaluated without exposing the animals to any other pain. Post-dose results at 3h, 6h and 24h following injection were compared to pre-dose levels.

Results: At 3h and 6h post-dose both buprenorphine formulations showed a significant analgesic effect compared to baseline. At 6h the effect was more pronounced in rats that had received the depot injection. At 24h, only the depot formulation still showed a significant effect. Saline did not alter the sensitivity to the pressure test at any time-point.

Conclusion: A human prolonged-release buprenorphine formulation (Buvidal) available in Europe has long-term analgesic effect in rats (up to 24h), as evaluated using the von Frey pressure test. This formulation should be considered as an alternative to multiple injections of short-acting buprenorphine formulations in rat studies where opioid analgesia is desired.