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.
Pucilowski
O
O
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Kostowski
W
W
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D002121:Calcium Channel Blockers; D011954:Receptors, Dopamine; D000431:Ethanol; D004110:Diltiazem; D006220:Haloperidol; D001058:Apomorphine