Atypical antipsychotics,clozapine and sulpiride do not antagonise amphetamine-induced stereotyped locomotion

An automated tracking system which converted an animal's path between quadrants of a circular open field into a series of trips was used to analyse stereotyped locomotion in amphetamine treated rats. Amphetamine (3.5 mg/kg) increased the horizontal distance moved and the number and proportion of thigmotaxic trips around the perimeter of the apparatus (length 4 trips). To investigate the hypothesis that classic antipsychotics, but not atypical antipsychotics, would antagonise the repetitive boundary patrolling associated with amphetamine-induced hyperactivity, animals were pretreated with haloperidol (0.01, 0.025, 0.05, 0.075 mg/kg), clozapine (5, 10, 20 mg/kg) or (±)sulpiride (10, 20, 50 mg/kg) 30 min before 3.5 mg/kg amphetamine. The results showed that the classic antipsychotic haloperidol antagonised both hyperactivity and the increased proportion of length 4 trips. In marked contrast, the atypical antipsychotics clozapine and sulpiride antagonised hyperactivity but did not reduce the proportion of length 4 trips. The inability of atypical antipsychotics to reduce the repetitive boundary patrolling associated with amphetamine-induced hyperactivity is consistent with the action of these drugs on other forms of amphetamine-induced stereotyped behaviour, and indicates that locomotor routes under amphetamine are stereotyped. The measurement of trip lengths provides a sensitive tool for examining drug action on the spatial distribution of open field locomotion.