D. Charrier et al., FAILURE OF CCK RECEPTOR LIGANDS TO MODIFY ANXIETY-RELATED BEHAVIORAL SUPPRESSION IN AN OPERANT CONFLICT PARADIGM IN RATS, Psychopharmacology, 121(1), 1995, pp. 127-134
The effects of cholecystokinin (CCK) receptor ligands were studied in
the rat safety signal withdrawal conflict procedure, an operant paradi
gm sensitive to both anxiolytic and anxiogenic compounds. In this proc
edure, behavioural suppression of lever pressing for food was induced
by the withdrawal of a conditioned signal for safety without the usual
presentation of a conditioned signal for danger. The compounds tested
were selective CCK-B antagonists [CI-988 (0.01-1 mg/kg SC), L-365,260
(0.0042 mg/kg IF) and LY 262,691 (0.001-1 mg/kg SC)], CCK-B agonists
[CCK-4 (0.01-1 mg/kg SC) and BC 264 (0.004-2 mg/kg IP)] and CCK-A anta
gonists [devazepide (0.001-1 mg/kg SC) and lorglumide (0.01-1 mg/kg SC
)]. None of these drugs induced the expected behavioural effects, i.e.
an anxiolytic-like release of the behavioural suppression with CCK-B
and, possibly, CCK-A antagonists and/or a further reduction of lever p
ressing with CCK-B agonists, indicative of an anxiogenic-like potentia
l. In contrast, the established anxiolytic lorazepam (0.06-0.25 mg/kg
IP), as well as diazepam (2 mg/kg IP) and buspirone (0.25mg/kg SC) use
d as positive control drugs, released the suppression of pressing for
food during the period associated with the safety signal withdrawal, w
hereas picrotoxin(1 mg/kg IF), used as an anxiogenic control, further
reduced responding during this conflict period. The present results co
ntrast with a series of published data suggesting the involvement of C
CK processes in anxiety-related behaviour in rodent models such as the
elevated plus-maze or the light:dark two compartment test, and in pan
ic disorders in humans. They indicate that the behavioural effects of
one category of drugs might vary considerably, depending on the experi
mental situation. Furthermore, they allow the conclusion that anticipa
tory anxiety generated by withdrawal of conditioned signals for safety
does not involve CCK-related processes.