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Psychopharmacology (Berl). 2001 Feb;154(1):1-7.

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

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  • 1Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, University of California, Los Angeles 90024, USA.

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.

PMID:
11291998
[PubMed - indexed for MEDLINE]
PMCID:
PMC2288655
Free PMC Article

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