Contralateral circling behaviour induced by intranigral injection of morphine and enkephalin analogue FK 33-824 in rats

Abstract

Contralateral circling behaviour induced by intranigral injection of morphine or an enkephalin analogue, FK 33-824, was studied in rats. Both morphine (0.625-10.0 micrograms) and FK 33-824 (1.25-40.0 ng) evoked the same kind of contralateral circling behaviour when injected into the substantia nigra. FK 33-824 was about 1000 times more potent than morphine and its effect lasted a little longer. Pretreatment with naloxone (5 mg/kg subcutaneously or 1 microgram intranigrally) almost completely blocked the circling induced by intranigral morphine or FK 33-824. The lesion of the ipsilateral nigrostriatal dopaminergic pathway with 6-hydroxydopamine significantly antagonized both morphine- and FK 33-824-induced circling. Pretreatment with d-amphetamine (1 mg/kg intraperitoneally) significantly increased the intensity of the circling induced by morphine or FK 33-824, and pretreatment with haloperidol (0.5 mg/kg subcutaneously) attenuated this intensity. Pretreatment with pilocarpine (10 mg/kg intraperitoneally) or mecamylamine (2 mg/kg intraperitoneally) inhibited the circling, whereas pretreatment with atropine (10 mg/kg intraperitoneally) or nicotine (0.2 mg/kg subcutaneously) increased morphine- and FK 33-824-induced circling. Pretreatment with muscimol (0.5 mg/kg subcutaneously) did not significantly increase morphine-induced circling but tended to increase FK 33-824-induced circling. Pretreatment with bicuculline (3 mg/kg intraperitoneally) slightly but significantly inhibited both morphine- and FK 33-824-induced circling. Pretreatment with strychnine (0.25 mg/kg intraperitoneally) did not modify the circling induced by morphine or FK 33-824. The results show that the contralateral circling behaviour induced by intranigral injection of morphine and FK 33-824 seems to be mediated by the activation of the dopaminergic nigrostriatal system.