Cholecystokinin receptor agonists block the jumping behaviour precipitated in morphine-dependent mice by naloxone

Abstract

The aim of present study was to reveal the role of cholecystokinin (CCK) in the jumping behaviour induced by the opioid antagonist naloxone (30 mg/kg) after the acute administration of morphine (200 mg/kg) in mice. Treatment with caerulein (0.01–1 μg/kg), a nonselective agonist of CCK receptors, induced a large reduction of jumping frequency without parallel suppression of locomotor activity. The CCK B receptor agonist CCK tetrapeptide (CCK-4, 0.125–32 mg/kg) caused the same effect, but it happened at much higher doses (above 0.5 mg/kg). Devazepide (1 μg/kg), a preferential CCK A receptor antagonist, completely reversed the action of caerulein (0.1 gmg/kg) and CCK-4 (2 mg/kg). A preferential CCK B receptor antagonists LY 288,513 at a high dose (4 mg/kg) blocked the action of CCK-4, but not that of caerulein. Acetorphan (16–128 mg/kg), an inhibitor of enkephalin metabolism, did not block naloxone-precipitated jumping behaviour. However, the combination of subthreshold doses of caerulein (0.001 μg/kg) and CCK-4 (0.25 mg/kg) with acetorphan (64 mg/kg) potently antagonized the behaviour induced by naloxone. In conclusion, the antagonism of CCK agonists against naloxone-precipitated jumping behaviour is apparently mediated via the CCK A receptor subtype. The stimulation of CCK A receptors seems to increase the release of endogenous enkephalins.