Central d-Ala super(2)-Met super(5)-enkephalinamide mu / delta -opioid receptor activation reverses the anxiogenic-like properties of cholecystokinin on locomotor and rearing activity in CD-1 mice

There is evidence to suggest an antagonistic interaction between the anxiogenic peptide, cholecystokinin (CCK) and the anxiolytic opioid peptide, enkephalin in mesolimbic sites following stressor applications in humans and animals which may define specific behavioral symptom subsets and alter the course of anxiety-like behavior. Locomotor and rearing behavior were decreased following a central CCK-8S (50 ng) injection among independent groups of mice relative to saline-treated animals. Central administration of DALA not only ameliorated the CCK-induced behavioral deficits but exaggerated behavioral activity of CCK and saline control mice (SAL). Locomotor activity and rearing behavior were depressed 24 h following DALA administration yet returned to basal values 168 h following drug applications. Eighteen days following the initial 50 ng CCK-8S and intervening DALA challenge, mice were administered 5 ng CCK-8S. An intervening dose of DALA in mice following the original 50 ng CCK-8S administration on Day 1 was associated with elevated locomotor activity in mice in response to the 5 ng CCK-8S challenge on Day 18. In contrast to locomotor activity, mice administered DALA following the original 50 ng CCK-8S administration on Day 1 demonstrated decreased rearing behavior to both 5 ng CCK-8S challenge and SAL on Day 18. Moreover, administration of 5 ng CCK-8S on Day 18 was associated with decreased rearing behavior in mice previously administered SAL on Day 1. These data imply that while CCK induces relatively protracted behavioral disturbances, mu / delta receptor activation may change the course of psychopathology.