The time course of the behavioral effects of amphetamine and their reversal by haloperidol in a primate species.

A group of six marmosets was administered amphetamine (Phase I), amphetamine plus haloperidol (Phase II), and then amphetamine alone (Phase III) over consecutive periods of 27, 51, and 33 days after which drug treatment was terminated (Phase IV). The animals' behavior was monitored during these periods and during a predrug treatment control period. Five mutually exclusive categories of behavior were assessed during the experiment. Social contact between animals was significantly suppressed and inactivity was increased throughout Phases I--III but both measures returned to normal values during Phase IV. Locomotion was significantly decreased towards the end of Phase I and initially during Phase II. Rapid head movements (termed checking) were significantly increased at the beginning of Phase I and again when the haloperidol was withdrawn at the beginning of Phase III. Towards the end of Phase I the animals developed destructive self-grooming habits. The time course of the effects of amphetamine and haloperidol on the different behavioral categories suggests that different mechanisms may be involved in each case. Viewed as a model of schizophrenia, the time course of haloperidol in reversing amphetamine-induced suppression of locomotion most closely resembles the time course of the antipsychotic effect of neuroleptics in man. Some effects of amphetamine (e.g., suppression of social interaction) are not reversed by haloperidol, and some effects of withdrawal of haloperidol (e.g., precipitation of checking movements not present when haloperidol was commenced) do not have an obvious counterpart in the clinical situation.