Targeted mutation of CCK2 receptor gene antagonises behavioural changes induced by social isolation in female, but not in male mice

Neuropeptide cholecystokinin (CCK) regulates the adaptation of rodents in the novel environment. In the present study we analysed the behavioural changes induced by the individual housing in mice, lacking CCK2 receptors. The wild-type (+/+) and homozygous (-/-) CCK2 receptor deficient mice of both gender were used throughout the study. The weight gain during the 21-day isolation period and changes in the locomotor activity following the social separation were measured. The elevated plus-maze and resident/intruder tests were also performed to test alterations in the emotional behaviour. Social isolation induced locomotor hyperactivity, reduced weight gain and increased aggressiveness in the wild-type (+/+) and homozygous (-/-) male mice. In the wild-type (+/+) female mice the significant reduction of exploratory activity in the plus-maze was evident. By contrast, in female mice, lacking CCK2 receptors, the exploration of the plus-maze was not significantly affected by the individual housing. This finding demonstrates that the social isolation does not cause anxiety-like state in the CCK2 receptor deficient mice. Moreover, the targeted invalidation of CCK2 receptors increased in male mice the affinity of dopamine D-2 receptors in the sub-cortical structures, whereas in female mice the increased affinity of 5-hydroxytryptamine(2) (5-HT2) receptors in the frontal cortex was established. The increased affinity of 5-HT2 receptors is probably the compensatory change to the lack of CCK2 receptors in female mice and probably reflects the reduced sensitivity of these animals to the anxiogenic manipulations. In conclusion, targeted mutation of CCK2 receptors selectively antagonised the behavioural changes induced by the individual housing in females, but not in male mice. (C) 2004 Elsevier B.V. All rights reserved.