Anxiety-like behavior and locomotion in CCK 1 knockout rats as a function of strain, sex and early maternal environment

Abstract

CCK is a peptide broadly distributed in the brain that is involved in the regulation of emotional behaviors through its binding to CCK 1 and CCK 2 receptors. Research has shown altered emotional and activity phenotypes in (male) Otsuka Long Evans Tokushima Fatty (OLETF) rats that lack CCK 1 receptors. In the present study, we examined anxiety-like behaviors, locomotion and corticosterone levels in OLETF and control (Long Evans Tokushima Otsuka (LETO)) strains (Experiment 1), and after cross-fostering and in-fostering conditions (Experiment 2), in males and females. The aim was to examine the early maternal contribution to the offspring's behaviors as examined in the elevated plus-maze and open-field paradigms. The results suggest a genetic/prenatal predisposition to moderate anxiety-like behaviors in the OLETF strain, especially in the males. Cross-fostering OLETF females to LETO dams significantly improved their performance both in the open field and the elevated plus maze. Hypo-locomotion was evident in OLETF rats of both sexes and remained unchanged regardless of the rearing conditions. LETO rats’ behavior was not affected by cross-fostering. Basal corticosterone levels remained similar among all groups at weaning and adulthood. The improvement in the OLETF strain's overall performance after adoption suggests a maternal contribution to the altered phenotype of these rats. The findings demonstrated the contribution of genetics, sex and early maternal environment to anxiety-like behaviors and locomotion in CCK 1 knockout rats, suggesting in addition to locomotion-reduction, the mutation may predispose the animals (rather than directly induce) to a moderate anxious phenotype.