Differential behavioural effect of quinpirole in neuroleptic-pretreated rats - role of alpha(1)-adrenoceptor

This paper presents the effect of 14-day intraperitoneal (i.p.) neuroleptic treatment on the behavioural response of Wistar rats to (-)-quinpirole hyd rochloride (3 mg/kg, i.p.) administered 24 h after the last neuroleptic dos e. Chlorpromazine hydrochloride (10 mg/kg), haloperidol (2 mg/kg) or (+/-)- sulpiride (100 mg/kg) increased the effect of quinpirole; however, there we re qualitative and quantitative differences between the neuroleptics. Chlor promazine and haloperidol, but not sulpiride, pretreatment enhanced quinpir ole-induced locomotor hyperactivity. Prazosin (0.5 mg/kg, i.p.) given to ch lorpromazine-treated rats 1 h before quinpirole attenuated the quinpirole-i nduced hyperlocomotion. In chlorpromazine-pretreated rats, quinpirole elici ted defensive aggressive behaviour with vocalization, copulatory attempts, intense rearing and head-down sniffing. When prazosin was given before quin pirole, head-down sniffing and object-directed oral activity were mainly ob served. In haloperidol-pretreated rats, quinpirole induced intense head-dow n sniffing, rearing, grooming and object-directed oral activity. In sulpiri de-pretreated rats, quinpirole induced intense head-down sniffing, grooming and object-directed oral activity. The results of the study suggest that d ifferences in the behavioural expression of dopamine D-2 receptor supersens itivity induced by neuroleptics may be, at least in part, caused by concurr ent stimulation of alpha(1)-adrenoceptors. (C) 1999 Elsevier Science B.V. A ll rights reserved.