Opioid antagonist naloxone potentiates anxiogenic-like action of cholecystokinin agonists in elevated plus-maze.
This study investigated the interplay of cholecystokinin (CCK) and endogenous opioid peptides in the regulation of anxiety. The acute administration of non-selective CCK agonist caerulein (1 and 5 microg/kg) and a selective CCK(B) receptor agonist BOC-CCK-4 (1, 10 and 50 microg/kg) induced a dose-dependent anxiogenic-like action in the plus-maze model of anxiety. BOC-CCK-4 displayed a similar efficacy with caerulein, indicating that the described effect was mediated via CCK(B) receptor subtype. The opioid antagonist naloxone itself (0.5 mg/kg) did not change the exploratory activity of rats in the plus-maze. However, the combination of naloxone with the sub-effective doses of caerulein (1 microg/kg) and BOC-CCK-4 (1 microg/kg) induced a significant inhibition of exploratory behaviour in rats. Accordingly, CCK and endogenous opioid peptides have an antagonistic role in the exploratory model of anxiety in rats.
Kõks
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Department of Physiology, University of Tartu, Estonia. sulev.koks@ut.ee
Soosaar
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Võikar
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Volke
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Ustav
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Männistö
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Bourin
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Vasar
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D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000819:agonists*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000502:physiology; D013758:Tetragastrin / Q000031:analogs & derivatives / Q000494:pharmacology
D009292:Narcotic Antagonists; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; D009270:Naloxone; C063051:butyloxycarbonyl-tryptophyl-methionyl-aspartyl-phenylalaninamide; D002108:Ceruletide; D002766:Cholecystokinin