Evaluation of three doses of oral trazodone and their impact on handling, activity, and physiological parameters in rabbits: a prospective, blinded, randomized cross-over study.

No study has determined the minimal effective dose of trazodone required to induce behavioral changes and its safety profile in rabbits. Therefore, this study aimed to determine the minimal effective dose of trazodone to improve compliance to handling, and to evaluate associated changes in motor activity, physiological and arterial blood gas parameters. Eight intact female New Zealand White rabbits (2-month-old; 1.66 ± 0.12 kg) were included in this prospective, blinded, randomized cross-over study. After a 10-day acclimation, rabbits randomly received placebo or trazodone 10, 20 or 30 mg/kg orally (PLAC, TRAZ10, TRAZ20, TRAZ30) with a 1-week wash-out period. Compliance scoring (dynamic interactive visual analog scale; DIVAS), activity levels measured with accelerometry (T0-T600), physiological parameters (temperature, heart, and respiratory rates), and arterial blood gas parameters (up to T240) were evaluated. Compliance scores, accelerometry, physiological and arterial blood gas parameters and hypoxemia prevalence (PaO <60 mmHg) were analyzed using linear mixed models and Chi-squared tests, respectively (P<0.05). When compared with PLAC, DIVAS scores were significantly higher at T80-120, T40-120 and T120-200 in TRAZ10, TRAZ20 and TRAZ30 post-administration, respectively. When compared with baseline, DIVAS scores were significantly higher from T80-160, T40-240 and T80-200 in TRAZ10, TRAZ20 and TRAZ30, respectively. All other parameters were not significantly different. In TRAZ30, hypoxemia was observed in 2/8 rabbits (P=0.104). In conclusion, oral trazodone improved rabbit compliance at all studied dosages, especially 20 mg/kg improved rabbit compliance without decreasing motor activity or causing hypoxemia.