Rats rapidly develop tolerance to the locomotor-inhibiting effects of the novel neuropeptide orphanin FQ.

We examined the effects of intracerebroventricular (i.c.v.) administration of orphanin FQ (OFQ) on locomotor activity in rats. The rats were habituated to locomotor-testing boxes and then injected i.c.v. with OFQ (0 - 10 nmoles). Acute injections of OFQ produced dose-orderly reductions in horizontal locomotion and rearing activity. This suppression of motor activity was characterized by a disruption of balance and muscle control. Within minutes of i.c.v. injection of the higher doses of OFQ, the rats exhibited flaccid muscle tone. They each lay in an atypical posture, pressing the abdomen against the floor, and splaying the hindlimbs. When these rats locomoted, their gate was unsteady. They wobbled from side to side, and frequently fell over. Repeated daily injections of OFQ resulted in a rapid development of tolerance to the OFQ-induced suppression of locomotion and rearing activity. Tolerance to the observed impairments of motor control were also apparent. In the rats that were repeatedly treated with the highest dose (10 nmol) of OFQ, tolerance to the motoric effects was still apparent after 7 days without OFQ treatment.