Cocaine- and amphetamine-regulated transcript peptide (CART) in the central nucleus of amygdala potentiates behavioral and hormonal responses of the rat exposed to its predator

Since cocaine- and amphetamine-regulated transcript peptide (CART) regulates anxiety and stress in amygdala, we hypothesized that the peptide may also process negative psychological experience like fear. During acute exposure to a cat, the rat showed freezing behavior and subsequently, profound signs of anxiety in social interaction test, and elevated serum cortisol concentration. While these behavioral effects were potentiated by the intracerebroventricular (icv) and intra-central nucleus of amygdala (intra-CeA) administration of CART peptide, they were blocked by CART antibody. On the other hand, chronic exposure for 7 days resulted in a steady reduction in freezing, increase in social interaction index and restored cortisol levels. In these rats, the behavior resembled with that of the time matched control rats suggesting habituation. However, CART peptide treatment, via the icv or intra-CeA route, chronically for 7 days, prevented habituation; significant freezing behavior and anxiety were noticed in these rats. The results suggest that CART peptide, in the framework of CeA, may process predator triggered innate fear in acute time scale, while chronic exposure might down-regulate the system and produce habituation.

► Acute exposure to predator produced fear and anxiety in rats.
► CART treatment by icv or intra-CeA potentiated the fear related behavior in rats.
► While chronic predator exposure developed tolerance to fear and anxiety, CART prevented the effect.
► Acute predator exposure increased serum cortisol concentration; chronic exposure had no effect.