A heparin derived oligosaccharide normalizes the fear response of old Brown Norway rats

Abstract

Old animals exhibit impaired spatial learning and an exaggerated response to stress. It was predicted that the heparin derived oligosaccharide (HDO), C3, would reverse these age-related deficits. Young (4–5 months) and old (19–20 months) Brown Norway male rats ingested C3 (25 mg/kg per day, p.o.) or vehicle (drinking water) daily for 42–44 days. Two weeks after the initiation of drug treatment, the rats were examined using a series of behavioral tests. The old control rats evidenced: (1) increased neophobia and reduced exploratory behavior in a novel open field (OF); and (2) exaggerated freezing during the acquisition and retention of a conditioned response (CR) to a Pavlovian light-shock pairing (“foreground” conditioning). C3 treatment attenuated or reversed this age-related impairment of emotional behavior. Analysis of spatial learning using the Morris water maze (MWM), and of CR formation to the place in which the foreground conditioning was conducted (“background” conditioning) during context dependent fear conditioning (CDFC) did not reveal major age or drug effects on memory processes. It is hypothesized that C3 repairs damage to the extracellular matrix (ECM) that occurs during the aging process and thereby normalizes age-related exacerbated fear behaviors without affecting mnestic processes.