Cholecystokinin accelerates the rate of habituation to a novel environment

Cholecystokinin (CCK8), an octapeptide present in high concentrations in both gut and brain, has been proposed as a putative satiety signal in a variety of species. Exploratory and social behaviors in particular are inhibited by exogenously administered CCK8. One hypothesis for the mechanism by which CCK reduces feeding and exploration is that CCK8 is reducing arousal and attention to environmental stimuli. This possibility was tested by analyzing the rate of habituation to the novelty of objects placed in an unfamiliar arena. A video-tracking computer-assisted animal behavior monitor measured four parameters of exploratory behaviors in rats pretreated with intraperitoneal CCK8. During the first 30 minutes in the novel environment, CCK8-treated animals showed a reduced latency to cessation of exploration as compared to saline controls. In repeated five minute sessions on consecutive days, CCK8 treatment accelerated the decline in exploration over daily sessions. Pentobarbital, a known sedative, induced low levels of exploration throughout the repeated daily sessions. These data suggest that CCK8 is inducing a more rapid rate of habituation to the novelty of environmental stimuli. An accelerated rate of habituation might underlie some of the satiety-related behavioral effects of this peptide.