Abstract
Previous studies suggest that cholecystokinin (CCK) is implicated in the modulation of pain sensitivity and memory functions. We used CCK2 receptor deficient homozygous (-/-) and heterozygous (+/-) mice and their wild type (+/+) littermates of 129sv/C57BL6 background and assessed their pain sensitivity and learning abilities in two different learning paradigms: passive avoidance test and Morris water maze. It has been found that mice without CCK2 receptors display hyposensitivity in Von Frey filament test and in plantar analgesia test and impaired memory functions in Y-maze paradigm. We found that in passive avoidance test, CCK2 receptor deficient -/- and +/- mice showed normal learning abilities compared to +/+ mice, if electric shocks of higher magnitude (0.4 mA or 0.6 mA for 2 s) were used, but displayed almost twice shorter entrance latencies (indicative of impaired memory) on Day 2 in case an electric shock of 0.2 mA for 2 s was used on Day 1. On Day 9 (long-term memory test), +/+ mice, subjected to stronger (0.4 mA or 0.6 mA for 2 s) electric shocks on Day 1, displayed somewhat decreased latencies, but the memory of -/- and +/- mice had even improved compared to Day 2. In Morris water maze, we established no statistically significant differences between -/-, +/- and +/+ CCK2 receptor deficient mice in neither the speed of learning, short-term memory (1 day and 5 days), nor long-term memory (14 days). Thus, the partly impaired performance of -/- and +/- mice in passive avoidance test (0.2 mA) can be explained by lower pain sensitivity, not impaired memory functions, because in three other conditions (passive avoidance with 0.4 mA and 0.6 mA, Morris water maze) no differences were established between the genotypes. The results are in good concordance with earlier experiments showing that CCK2 receptor deficient mice have lower pain sensitivity, but do not support previous studies that have established impaired memory functions in CCK2 receptor deficient mice.