Physiological effect of trazodone hydrochloride use for anxiety and sedation in rabbits (Oryctolagus cuniculus)

Abstract

Oral sedation options for rabbits (Oryctolagus cuniculus) have remained limited despite the need for medications with anxiolytic effects during transportation and high stress procedures. Trazodone HCl (TZN), a serotonin modulator, is a commonly prescribed medication in humans to treat depression and anxiety. The efficacy of TZN use in rabbits was initially investigated in 2016 and found TZN to be successful in producing mild sedation, however the safety of the medication still needed to be determined. To identify the systemic effects of repeated TZN administration in rabbits, New Zealand white laboratory rabbits (n = 12) were given orally 40 mg/kg TZN every 12 hours (± 1 hour) for 28 days. A control group (n = 4) was used to monitor standard hematological fluctuations. Heart and respiratory rate were collected daily, and a physical examination was performed by a veterinarian every 7 days. Blood was collected for cell counts and serum chemistry analysis prior to and every 14 days during the experiment. No significant changes in heart or respiratory rate were noted throughout treatment (p = 0.201 and p = 0.984 respectively). Some fluctuations were noticed in blood serum chemistry and hematology results in both the experimental and control group, particularly in the liver and kidney values following 28 days of treatment. Serum alanine aminotransferase (ALT) between the blood draws of both groups was significantly elevated (p = 0.002), however the elevations were noticed in both the control and TZN treated animals (p = 0.597). A simmilar trend was noticed with alkaline phosphatase (ALP; p = 0.001 between blood draws, p = 0.428 between groups), creatinine (p < 0.0001 between blood draws, p = 0.340 between groups), and blood urea nitrogen (BUN) levels (p = 0.025 between blood draws, p = 0.343 between groups) indicating the changes overtime were not due to TZN treatment. All physiologic parameters tested remained within normal rabbit physiologic reference ranges. These results indicate TZN could be a viable option to provide mild sedation as needed and act as an alternative option to conventional treatments of behavioral problems. Future studies could be performed on dose range and safety among rabbits of varying age, sex, and breed.