BOC-CCK-4, CCK(B)receptor agonist, antagonizes anxiolytic-like action of morphine in elevated plus-maze
by
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

ABSTRACT

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

DAMGO
Arrestin
Dynamin
G protein
Morphine
Tramadol
Proglumide
Mechanisms
Peroxynitrite
Cholecystokinin
Novelty and pain
Receptor regulation
Glycine anatagonists
Fentanyl and ketamine
Behavioral senstization
Opioids, mood and cognition
Morphine, naltrexone and tolerance
Tolerance, sensitization and dependence
The molecular mechanisms of opioid tolerance

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