Diltiazem suppresses apomorphine-induced fighting and pro-aggressive effect of withdrawal from chronic ethanol or haloperidol in rats.

Dopaminergic receptor stimulation with apomorphine (5 mg/kg, i.p.) induced irritable aggression consisting of defensive upright postures, vocalization and biting attacks in pairs of responsive rats. Aggression was considerably decreased when the animals were pretreated with diltiazem, a Ca2+ channel inhibitor (5 or 10 mg/kg, i.p.). Originally non-responsive rats exhibited apomorphine-induced fighting upon withdrawal from prolonged ethanol (21 days, 3 g/kg, twice daily, intragastrically, i.g.) or haloperidol (14 days, 0.5 mg/kg, twice daily i.g.). If the animals were co-administered diltiazem i.g. 30 min prior to each dose of ethanol or haloperidol the aggressive response to apomorphine was significantly decreased; reduction in attack score being the most prominent. Chronic (14 or 21 days) diltiazem by itself did not facilitate the appearance of apomorphine-induced fighting in non-responsive rats. These results suggest that diltiazem can inhibit apomorphine-induced fighting and prevent the development of ethanol and haloperidol-induced behavioural supersensitivity to apomorphine.