Dopaminergic supersensitivity in rats with a repeated administration of haloperidol: Studies on stereotypy and locomotor activity

Rats were pretreated daily with haloperidol (0.5 mg/kg i.p., twice a day) for 2 weeks and thereafter tested for alterations in dopamine(DA)-mediated behavior. 1) The above pretreatment abolished the hypomotility induced by low doses of lisuride and apomorphine and potentiated the hyperactivity induced by medium doses of the two agents. 2) The pretreatment raised the intensity of lisuride- and apomorphine-induced sniffing, which was antagonized by sulpiride. On the other hand, apomorphine-induced licking showed no interference by the haloperidol pretreatment and with a further injection of sulpiride. However, both the two patterns of stereotyped behavior in response to apomorphine disappeared in the presence of haloperidol. 3) Lisuride caused the stereotyped licking only under the complete inhibition by sulpiride of sniffing. These results suggest existence of two types of postsynaptic DA receptors in mesolymbic and nigrostriatal systems; one, which is susceptible to sulpiride, is involved in locomotion and sniffing, and the other is involved in licking. Furthermore, it is concluded that the pretreatment with haloperidol leads to a preferential induction of supersensitivity in the former receptor.