The atypical antipsychotic drug, aripiprazole, reverses amphetamine‐induced focused stereotypy in rats

Abstract

Although the dopamine D2 partial agonist and atypical antipsychotic drug (AAPD), aripiprazole (ARPZ), has been shown to antagonize apomorphine‐induced behaviors in rats, it is unknown whether ARPZ antagonizes amphetamine (AMPH)‐induced behaviors in this species. Accordingly, this study examined effects of ARPZ on AMPH‐induced focused stereotypy in rats. Clozapine was included as a comparison AAPD. Rats were first sensitized to AMPH by 5 treatments (5.0 mg/kg, ip.) each separated by 72 hr. Subsequently, AMPH treatments continued but were followed 30 min later by ARPZ (6, 12, and 18 mg/kg, po.) or clozapine (5, 10, 20 mg/kg, po.). Focused stereotypy and locomotor activity were quantified with force‐plate actometers in 4‐hr recording sessions. Clozapine prolonged AMPH‐induced focused stereotypy and slowed the rats’ rhythmic head movements. On the other hand, ARPZ significantly reversed the expression of focused stereotypy and left intact intermediate amounts of locomotion. Thus, ARPZ behaviorally antagonized the effects of the indirect‐acting dopamine agonist AMPH, and this effect is consistent with ARPZ's D2 partial agonist properties. Supported by MH043429 & HD002528.