Effects of administration regime on the psychotomimetic properties of d-amphetamine in the squirrel monkey (Saimiri sciureus)

Studies have reported that d-amphetamine can induce a schizophreniform psychosis in humans and can induce abnormal behaviour patterns in monkeys that resemble the psychotic symptoms observed in man. The purpose of the present study was to identify a drug administration regime that in squirrel monkeys reliably could induce such behaviours in order to use this as a model of schizophrenia. The behavioural effects of acute, subchronic and continuous administration of d-amphetamine were determined in male and female squirrel monkeys during short term separation from the colony and in the home cage. It was found that abnormal behaviours developed in both male and female subjects and that they were most evident in the home cage. The number of subjects responding was highest during continuous infusion followed by subchronic treatment. The study indicated that prolonged administration of high doses of d-amphetamine is necessary for the development of abnormal behaviours. These findings suggest that animal models of schizophrenia based on d-amphetamine should be based on chronic administration or continuous infusion of d-amphetamine instead of acute injections.