EVALUATION OF LYTHRINE, AN ALKALOID FROM HEIMIA SALICIFOLIA, IN AN AVIAN MODEL OF ANXIETY AND DEPRESSION

The purpose of this thesis was to evaluate whether an acute exposure to lythrine, a naturally occurring alkaloid substance from Heimia salicifolia, has anxiolytic properties in a validated avian model of anxiety and depression. Socially raised, five-day-old chicks were exposed to an isolation stressor for five minutes after receiving one of five treatments. These were: 1) vehicle-treated, 2) clonidine (0.1 mg/kg body weight), and 3) lythrine-treated groups at each of the different dosages (0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg). All lythrine treatment doses were dissolved in 10% cremaphor, 5% ethanol, and 85% deionized water. A solution of exclusively 10% cremaphor, 5% ethanol, and 85% deionized water served as the vehicle-group. Clonidine was dissolved in saline and served as our known anxiolytic positive control comparison. During the exposure to isolation stressor, distress vocalizations (DVocs) of the chicks were recorded. Vehicle treated animals displayed high rates of DVocs indicative of a panic state and consistent with previous findings in this model. Clonidine-treated animals displayed a reduced rate of DVocs, indicative of an anti-panic (i.e. anxiolytic) effect. All three lythrine doses failed to attenuate panic, as measured by a failure to reduce DVocs in the five-minute isolation test. The findings from this study suggest that at the doses tested lythrine does not possess anti-panic (i.e. anxiolytic) effects. However, limitations include the low dosing as well as housing maintenance issues. For this study, we chose low doses based upon lythrine’s limited availability, novelty and limited in vivo testing of the compound, and clonidine’s active dosage. Future studies should evaluate both higher and lower doses of lythrine in this model to elucidate a dose-response curve while measuring potential anxiolytic effects. Additionally, further evaluation of lythrine’s pharmacokinetics and pharmacodynamics is needed.