An ethopharmacological assessment of the effects of zuclopenthixol on agonistic interactions in male mice

Zuclopenthixol is a thioxanthene derivative which acts as a mixed dopamine D-1/D-2 receptor antagonist. Although the antiaggressive action of neurolep tic drugs is well known, the effects of zuclopenthixol on agonistic interac tions have not been explored and there ae no studies comparing acute and su bchronic effects of this compound oil aggression in rodents. In this work, we examined the action of zuclopenthixol (0.025-0.4 mg/kg), administered ac utely ol subchronically for 10 days, on agonistic behavior elicited by isol ation in male mice. Individually housed mice were exposed to anosmic "stand ard opponents" 30 min after the drug administration, and encounters were vi deotaped and evaluated using an ethologically based analysis. After acute t reatment, zuclopenthixol (0.2 and 0.4 mg/kg)-treated animals exhibited etho pharmacological profiles characterized by a decrease in offensive behaviors without impairment of motor activity (0.2 mg/kg). In contrast, the antiagg ressive action of the highest dose used (0.4 mg/kg) was accompanied by a ma rked increase of immobility. After subchronic treatment, no tolerance to zu clopenthixol antiaggressive or motor activity was observed. Overall, this b ehavioral profile is similar to that observed with other typical neurolepti cs. (C) 1999 Prous Science. All rights reserved.