RATS RAPIDLY DEVELOP TOLERANCE TO THE LOCOMOTOR-INHIBITING EFFECTS OFTHE NOVEL NEUROPEPTIDE ORPHANIN FQ

We examined the effects of intracerebroventricular (i.c.v.) administra tion of orphanin FQ (OFQ) on locomotor activity in rats. The rats were habituated to locomotor-testing boxes and then injected i.c.v. with O FQ (0 - 10 nmoles). Acute injections of OFQ produced dose-orderly redu ctions in horizontal locomotion and rearing activity. This suppression of motor activity was characterized by a disruption of balance and mu scle control. Within minutes of i.c.v. injection of the higher doses o f OFQ, the rats exhibited flaccid muscle tone. They each lay in an aty pical posture, pressing the abdomen against the floor, and splaying th e hindlimbs. When these rats locomoted, their gate was unsteady. They wobbled from side to side, and frequently fell over. Repeated daily in jections of OFQ resulted in a rapid development of tolerance to the OF Q-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 O FQ, tolerance to the motoric effects was still apparent after 7 days w ithout OFQ treatment.