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

Abstract

Rationale: Orphanin FQ (OFQ; also known as nociceptin), the endogenous ligand 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 present study was designed to determine if OFQ similarly attenuates cocaine-induced motor stimulation and to determine if this effect is dependent on attenuation of the increase in extracellular DA.

Methods: After a 1-h adaptation period, rats were injected with either artificial cerebrospinal fluid or OFQ (3-30 nmol, i.c.v.) 5 min prior to cocaine (10 mg/kg, i.p.) or apomorphine (3 mg/kg, i.p.) administration and the total distance traveled was measured for a further 1 h. In a separate experiment, changes in extracellular 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 both the basal and the cocaine-induced increase in extracellular DA in the Nuc Acc. OFQ, at the highest dose, also decreased the motor stimulation induced by apomorphine.

Conclusions: Our results suggest that the modulatory effect of OFQ on locomotor activity is not solely due to its inhibitory action on extracellular DA in the Nuc Acc.

Fig. 1

Orphanin FQ (OFQ) dose-dependently [3, 10, or 30 nmol, intracerebroventricularly (i.c.v.)] attenuated the motor stimulatory effect of cocaine (10 mg/kg) or apomorphine (3 mg/kg). Data are means ± SEM. *Significantly different from the respective control group (cocaine experiment) (P<0.05; revealed by the post hoc Newman-Keuls test). **Significantly different from the respective control group (apomorphine and cocaine experiment) and OFQ (3 nmol)-treated group (cocaine experiment) (P<0.05; revealed by the post hoc Newman-Keuls test)

Fig. 2

OFQ (30 nmol, i.c.v.) attenuated the increase in nucleus accumbens (Nuc Acc) extracellular dopamine (DA) induced by cocaine (10 mg/kg, i.p.) in anesthetized rats. The arrow indicates the time of artificial cerebrospinal fluid (aCSF) or OFQ injection followed (5 min later) by cocaine administration. The first three time intervals are basal levels of DA and the sampling time was 15 min. Data are means ± SEM

Fig. 3

OFQ attenuated basal extracellular DA in the Nuc Acc in anesthetized rats. The arrow indicates the time of aCSF or OFQ administration. The first three time intervals are basal levels of DA and the sampling time was 15 min. Data are means ± SEM