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

Abstract

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.

YKP1447, A Novel Potential Atypical Antipsychotic Agent

“…The behavioral studies using rats, antagonism of dopamine agonist-induced hyperlocomotion (Janssen et al, 1965;Ogren et al, 1984;Gustafsson and Christensson, 1990;Moore and Kenyon, 1994) and conditioned avoidance response (CAR) paradigm (Cook et al, 1955;Davidson and Weidley, 1976;Arnt, 1982; for review, see Wadenberg et al, 1999) have traditionally been used to predict the antipsychotic efficacy of novel agent. In the present study, YKP1447 dose-dependently inhibited d-amphetamine-induced hyperlocomotion activity in rats, indicating the antipsychotic action of YKP1447.…”

Phencyclidine-induced increases in striatal neuron firing in behaving rats: reversal by haloperidol and clozapine

“…When administered to animals, these drugs elicit a pattern of repetitive behavior (stereotypy), which requires an intact dopaminergic projection to the striatum and other forebrain sites (Dunnett and Robbins, 1992;Rebec and Bashore, 1984). In fact, amphetamine not only releases striatal dopamine (Butcher et al, 1988;Kuczenski and Segal, 1989;Zetterstr6m et al, 1983), but the behavioral effects of this drug are blocked either by neuroleptics (e.g., Megens et al, 1992;Moore and Kenyon, 1994;Ridley et al, 1979;Rollema et al, 1976;Tschanz and Rebec, 1988), which block dopamine receptors (Ellenbroek, 1993;Reynolds, 1994;Seeman, 1980), or by destruction of dopaminergic terminals in the striatum (Creese and Iversen, 1975;Fibiger et al, 1973;Fink and Smith, 1980;Kelly et al, 1975). Thus, stria.tal dopamine has been linked not only to the behavioral effects of amphetamine but also to idiopathic schizophrenia (Carlsson, 1978;Laduron, 1989;Seeman and Van Tol, 1994).…”

Pharmacological actions of the atypical antipsychotic drug clozapine: A review

“…The locomotor stereotypy produced by methylphenidate and amfonelic acid is blocked by haloperidol, but not by CLOZ (Mueller, 1993). However, CLOZ has been reported to block selective components of amphetamine-induced stereotypy (Tschanz and Rebec, 1989), but does not antagonize amphetamine-induced stereotyped locomotion (Moore and Kenyon, 1994). It has been suggested that CLOZ produces catalepsy, although this effect is not dose-dependent and is not very marked or intense (Costall and Naylor, 1975).…”