Orphanin FQ/nociceptin attenuates motor stimulation and changes in nucleusaccumbens extracellular dopamine induced by cocaine in rats

Rationale: Orphanin FQ (OFQ; also known as nociceptin), the endogenous liga nd of the opioid receptor-like receptor, injected intracerebroventricularly (i.c.v.) decreases basal motor activity and basal extracellular levels of dopamine (DA) in the nucleus accumbens (Nuc Acc) in rats. Objective: The pr esent study was designed to determine if OFQ similarly attenuates cocaine-i nduced motor stimulation and to determine if this effect is dependent on at tenuation of the increase in extracellular DA. Methods: After a l-h adaptat ion period, rats were injected with either artificial cerebrospinal fluid o r OFQ (3-30 nmol, i.c.v.) 5 min prior to cocaine (10 mg/kg, i.p.) or apomor phine (3 mg/kg, i.p.) administration and the total distance traveled was me asured for a further 1 h. In a separate experiment, changes in extracellula r DA were monitored by microdialysis following cocaine and OFQ treatment in anesthetized rats. Results: OFQ dose-dependently attenuated both basal and cocaine-induced motor stimulation. OFQ (30 nmol, i.c.v.) also attenuated b oth the basal and the cocaine-induced increase in extracellular DA in the N uc Ace. OFQ, at the highest dose, also decreased the motor stimulation indu ced by apomorphine. Conclusions: Our results suggest that the modulatory ef fect of OFQ on locomotor activity is not solely due to its inhibitory actio n on extracellular DA in the Nuc Ace.