CHOLECYSTOKININ RECEPTORS AND MEMORY - A RADIAL MAZE STUDY

CCK receptor agonists and antagonists have repeatedly been demonstrated to improve and impair, respectively, learning and memory functions. However, all studies to date have exploited avoidance paradigms. In the present study, the effect of some CCK receptor agonists and antagonists on the ability to learn an appetitively motivated task and to influence spatial working memory was investigated. In the first experiment, drugs were given immediately after each training session in the radial maze and the animals were tested, drug-free, during a 2-week period. After the initial treatments with caerulein, an unselective CCK receptor agonist (100 ng/kg SC), the animals were slightly less successful to obtain food pellets during the sessions on the first 2 days; whereas proglumide, an unselective CCK receptor antagonist (1 mg/kg SC) was without any effect. However, on the following days, all the three groups of rats (saline, caerulein, and proglumide) performed in a similar way. In the second experiment, drugs were given before each test session to well-trained animals. Scopolamine (0.15 and 0.3 mg/kg IP), the reference amnestic drug, produced dose-dependent impairment of working memory in the radial maze test. Proglumide (1 and 10 mg/kg SC) and devazepide, (a selective CCK-A receptor antagonist; 0.01 and 1 mg/kg SC), as well as caerulein (0.01, 0.1 and 1 mug/kg SC) and CCK-4 (a selective CCK-B receptor agonist; 25 and 50 mug/kg SC) had no reliable effect. When caerulein (0.1, 2 and 10 mug/kg SC) was given together with scopolamine (0.15 mg/kg IP), the lower doses were without effect, whereas the highest dose of the peptide tended to potentiate the action of scopolamine, probably due to its sedative action. On the other hand, the selective CCK-B receptor agonist CCK-4 (50 mug/kg SC), administered together with scopolamine (0.15 mg/kg IP), did not induce sedation, but caused a further increase in the number of erroneous arm entries and a changed pattern of arm exploration. Taken together, the results support the idea that the effects of CCK receptor ligands on learning and memory differ in aversively vs appetitively motivated paradigms and depend upon the receptor subtype activated or blocked.