BOC-CCK-4, CCK(B)receptor agonist, antagonizes anxiolytic-like action of morphine in elevated plus-maze
Koks S, Soosaar A, Voikar V, Bourin M, Vasar E
Department of Physiology,
University of Tartu,
Tartu, Estonia
Neuropeptides 1999 Feb; 33(1):63-69 1999 Sep;124(1):51-5


This study investigated a role of cholecystokinin (CCK) in the anxiolytic-like action of morphine, an agonist of mu-opioid receptors, in the rat plus-maze model of anxiety. The acute administration of morphine (1 mg/kg) induced a significant increase of exploratory activity in the plus-maze, but did not affect the locomotor activity in the motility test. The higher dose of morphine (2.5 mg/kg) tended to decrease the locomotor activity and, therefore, did not cause the anxiolytic-like action in the plus-maze. The other drugs (naloxone, BOC-CCK-4, L-365,260) and their combinations with morphine (0.5-1 mg/kg) did not affect the locomotor activity of rats. The opioid antagonist naloxone itself (0.5 mg/kg) did not change the exploratory activity in the plus-maze, but potently antagonized the anxiolytic-like action of morphine (1 mg/kg). An agonist of CCK(B)receptors BOC-CCK-4 (1-50 mug/kg) induced a dose-dependent anxiogenic-like action in the plus-maze. Nevertheless, only one dose of BOC-CCK-4 (10 mug/kg) completely reversed the action of morphine. Also, one dose of CCK(B)receptor antagonist L-365,260 (10 mug/kg) was effective to modify the behaviour of rats in the elevated plus-maze. Namely, this dose of L-365,260 increased the ratio between open and total arm entries, a behavioural measure believed to reflect the anxiolytic-like action in the elevated plus-maze. The combination of L-365,260 (100 mug/kg) with the sub-effective dose of morphine (0.5 mg/kg) caused the anxiolytic-like action in the plus-maze not seen if the drugs were given alone. In conclusion, morphine induces a potent anxiolytic-like action in the elevated plus-maze and CCK is acting as an endogenous antagonist of this effect of morphine
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