We present the results of a behavioural analysis of the effects of the neuroleptic drugs clozapine and risperidone in rhesus monkeys. The subjects for the study were social colonies of 3-5 year old adult rhesus monkey (Macaca mulatta) weighing 4-6 kg. Each colony comprised eight monkeys (one male and seven females). Only active healthy animals were accepted for the study. Each colony was housed in a 20' x 12' x 8' cage. The monkeys were kept under controlled temperature conditions (22±5°C), humidity and ventilation (with 100% fresh air) and light (12 hour light/dark cycle) to maintain their breeding and physiological rhythm. The light intensity was about 300 lux. A balanced diet was provided in the morning and evening and water was available ad libitum through an automatic watering system. Animals were allowed 4-6 weeks time to stabilise their behaviour in the new surroundings. To reduce the stress induced by handling and dosing, the animals were handled by a single experimenter. During the period of habituation, monkeys were caught and removed from the cage at least once a week and administered saline intramuscularly or orally.

Behavioural observations took place prior to (base-line control) and after drug or vehicle treatment. A checklist of social and solitary behavioural responses [1] modified from the parameters described by Schlemmer and Davis [2] was used. The behaviour was observed on a video monitor placed in an adjacent room with the help of two strategically placed 180° rotating video cameras, provided with zoom lens, fixed in the behaviour chamber. Behavioural responses were video taped for analysis and archiving. On any one day, only one animal from the group was injected with the drug and the behaviour was observed as described below. The other animals of the group were injected with the drug by rotation and score of normal behaviour compared with the behaviour after treatment. A minimum interval of 10 days was maintained between two doses of the drug to the same monkey in order to washout the effect of previous dose. Each monkey was observed in rotation for 1 minute at every 10 minutes for 2 hours initially as well as after drug or vehicle treatment. The scores of each behaviour from the twelve 1-minute intervals were summed up for individual animals and that represented the day's score for that monkey. The monkeys were also observed at 4, 6, 8 and 24 hours post treatment for any significant alteration in behaviour. Statistical analysis was performed for all behavioural data by using Mann-Whitney U test.

Clozapine (5-20 mg/kg, po) produced a decrease in social and solitary behaviour. In the highest dose (20 mg/kg, po) it produced a marked decrease in all social and solitary behaviours and catalepsy along with continuous salivation. Risperidone (025-0.2 mg/kg, po) showed a decrease in social and solitary behaviour. The highest dose (0.2 mg/kg, po) produced marked sedation only. It may be concluded on the basis of above findings that the profile of behavioural effects of risperidone is similar to that of clozapine in certain parameters but it has no extrapyramidal side effects and does not produce hypersalivation.

References

1. Palit et al. (1994)
2. Schlemmer; Davis (1983)