Antidepressant-like effects of CCKB antagonists in mice: antagonism by naltrindole.
1. The effects of selective CCKB agonists, BC 264 and BC 197 were investigated in the conditioned suppression of motility test in mice, an animal model used to select antidepressant drugs. The results showed that both CCKB agonists at doses of 3 and 30 micrograms kg-1, accentuated the suppression of motility in shocked mice and did not modify the behaviour of non-shocked mice. The effects of BC 264 were suppressed by L-365,260. 2. L-365,260 alone, at doses of 0.2 and 2 mg kg-1 decreased motor inhibition in shocked mice and had no effect in non-shocked mice. 3. The effects of L-365,260 observed in shocked mice were suppressed by naltrindole, a selective antagonist for delta-opioid receptors, suggesting the occurrence of physiological adverse interactions between CCK and opioid systems. 4. Together, these results suggest that CCKB antagonists could block centrally located CCKB receptors to produce antidepressant-like effects which could indirectly involve delta-opioid receptor stimulation.
Departement de Pharmacochimie Moléculaire et Structurale, INSERM U266, CNRS URA D 1500, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
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D000595:Amino Acid Sequence; D000818:Animals; D000928:Antidepressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000494:pharmacology; D003214:Conditioning, Classical; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology
D000928:Antidepressive Agents; C084553:BC 264; D001570:Benzodiazepinones; D010446:Peptide Fragments; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C060186:BC 197; C058121:L 365260; D009271:Naltrexone; D002766:Cholecystokinin; C055382:naltrindole