Anxiety-like behavior and locomotion in CCK1 knockout rats as a function of strain, sex and early maternal environment

CCK is a peptide broadly distributed in the brain that is involved in the regulation of emotional behaviors through its binding to CCK1 and CCK2 receptors. Research has shown altered emotional and activity phenotypes in (male) Otsuka Long Evans Tokushima Fatty (OLETF) rats that lack CCK1 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 CCK1 knockout rats, suggesting in addition to locomotion-reduction, the mutation may predispose the animals (rather than directly induce) to a moderate anxious phenotype.