Comparative effects of sertraline, haloperidol or olanzapine treatments on ketamine-induced changes in mouse behaviours

Effects of sertraline, haloperidol or olanzapine administration on ketamine-induced behaviours in mice were examined. The aim was to ascertain the degree of reversal of such behaviours by sertraline, and compare its effectiveness to haloperidol and olanzapine. Ten-week old mice (N = 120) were equally divided into main groups; 1 (open-field, radial-arm maze and elevated plus maze {EPM} tests), and 2 (social interaction test). Mice in each main group were assigned into six groups of ten (n = 10) each. Group 1 received intraperitoneal (i.p) injection of vehicle, while groups 2-6 received i.p ketamine at 15 mg/kg daily for 10 days. From day 11 to 24, mice in group 1 (vehicle) were given distilled water (i.p at 2 ml/kg and oral at 10 ml/kg), group 2 (ketamine control) received daily i.p ketamine and oral distilled water; while animals in groups 3-6 received daily i.p. ketamine and oral haloperidol (4 mg/kg), olanzapine (2 mg/kg), or one of two doses of sertraline (SERT) (2.5 or 5 mg/kg), respectively. Treatments were administered daily, and behaviours assessed on days 11 and 24. Results showed that repeated ketamine administration caused hyperlocomotion, increased self-grooming, memory loss and social withdrawal. Administration of sertraline (both doses), haloperidol, and olanzapine reversed ketamine-induced behavioural changes. However, in the EPM, sertraline and olanzapine were anxiolytic, while haloperidol was anxiogenic. Sertraline's effect on behaviours tested was comparable to olanzapine and better than haloperidol. In conclusion, this study shows that sertraline's ability to counteract ketamine-induced behavioural changes in mice is comparable to known antipsychotics.