Central administration of nociceptin/orphanin FQ blocks the acquisition of conditioned place preference to morphine and cocaine, but not conditioned place aversion to naloxone in mice.

RATIONALE

Previous studies have suggested that nociceptin (known also as orphanin FQ) suppresses the rewarding potential of morphine and alcohol in the rat. However, little is known of the effect of nociceptin on the rewarding properties of these and other drugs in the mouse.

OBJECTIVE

To determine the effect of nociceptin on opiate or psychostimulant-induced conditioned place preference, or naloxone-induced conditioned place aversion in mice.

METHODS

C57BL6 mice were implanted with chronically indwelling intracranial cannulae targeted at the lateral cerebroventricle through which nociceptin (0.06, 0.6, or 6 nmol) could be administered. Animals were conditioned in an unbiased balanced paradigm to study the effect of nociceptin administration alone, or the effect of nociceptin on the acquisition of place conditioning to morphine, cocaine, or naloxone (all 7.6 mg/kg subcutaneous).

RESULTS

Administration of 0.06 nmol nociceptin alone stimulated locomotion during conditioning sessions, but had no hedonic effects. In contrast, administration of 6 nmol nociceptin alone markedly reduced basal locomotion during the conditioning sessions and induced a mild place aversion. Both morphine and cocaine induced robust place preferences, the acquisition of which was dose dependently suppressed by administration of nociceptin at doses of 0.6 nmol and above. Conditioning with naloxone produced a robust place aversion that was only weakly blocked by the maximum dose of nociceptin tested.

CONCLUSION

Nociceptin blocks the rewarding properties of drugs in both narcotic analgesic and psychostimulant classes in the mouse. In contrast, nociceptin has only a minor effect on the negative affective state experienced following naloxone administration.