Guinea pigs (Cavia porcellus) are widely used in biomedical research and are sensitive to stress-induced anorexia and weight loss. Buprenorphine extended release (XR) is commonly used for analgesia in laboratory animals but has been associated with decreased appetite and weight loss. Capromorelin, a ghrelin receptor agonist, is FDA-approved to stimulate appetite in dogs and cats. However, its utility in mitigating opioid-associated weight loss in guinea pigs has not been evaluated. This study's primary objective was to evaluate the effects of capromorelin on body weight in guinea pigs, both independently and in conjunction with buprenorphine XR administration, and whether oral capromorelin mitigates the weight loss associated with buprenorphine administration. A secondary objective was to evaluate habituation to voluntary consumption of an oral delivery puree and continued consumption of the puree with capromorelin added. Forty-eight female guinea pigs were randomized into 4 groups (n = 12/group) in a 2 × 2 factorial design. Animals were acclimated for 5 days to receive oral treatments, and all received either oral capromorelin (5 mg/kg) or sham treatment daily for 3 days, combined with either a single subcutaneous dose of buprenorphine XR (0.48 mg/kg) or saline. Body weights were recorded days -7 through -3 and days 0 through 5. All animals accepted oral treatments without the need for oral gavage. Guinea pigs receiving buprenorphine XR experienced significant weight loss compared with controls and were significantly less likely to return to baseline weight. Capromorelin treatment did not significantly affect weight change, and no interaction between capromorelin and buprenorphine XR was observed. Therefore, capromorelin at 5 mg/kg once a day for 3 days did not mitigate weight loss associated with buprenorphine XR administration in guinea pigs. These findings emphasize the need for species-specific evaluation of appetite stimulants and support the value of extended monitoring following administration of long-acting analgesics.
Silvers et al. (Sun,) studied this question.