Differential behavioural effect of quinpirole in neuroleptic-pretreated rats — role of α 1-adrenoceptor

Abstract

This paper presents the effect of 14-day intraperitoneal (i.p.) neuroleptic treatment on the behavioural response of Wistar rats to (−)-quinpirole hydrochloride (3 mg/kg, i.p.) administered 24 h after the last neuroleptic dose. Chlorpromazine hydrochloride (10 mg/kg), haloperidol (2 mg/kg) or (±)-sulpiride (100 mg/kg) increased the effect of quinpirole; however, there were qualitative and quantitative differences between the neuroleptics. Chlorpromazine and haloperidol, but not sulpiride, pretreatment enhanced quinpirole-induced locomotor hyperactivity. Prazosin (0.5 mg/kg, i.p.) given to chlorpromazine-treated rats 1 h before quinpirole attenuated the quinpirole-induced hyperlocomotion. In chlorpromazine-pretreated rats, quinpirole elicited defensive aggressive behaviour with vocalization, copulatory attempts, intense rearing and head-down sniffing. When prazosin was given before quinpirole, head-down sniffing and object-directed oral activity were mainly observed. In haloperidol-pretreated rats, quinpirole induced intense head-down sniffing, rearing, grooming and object-directed oral activity. In sulpiride-pretreated rats, quinpirole induced intense head-down sniffing, grooming and object-directed oral activity. The results of the study suggest that differences in the behavioural expression of dopamine D 2 receptor supersensitivity induced by neuroleptics may be, at least in part, caused by concurrent stimulation of α 1-adrenoceptors.