BACKGROUND: The aim of this study was to investigate the effects of a potent nitric oxide-guanylate cyclase activator, 3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazole (YC-1), on learning and memory functions in aged rats.

MATERIAL AND METHODS: Rats were divided into 2 groups as 4-month-old and 24-month-old rats. Rats received YC-1 (1 mg/kg/day) for 2 weeks long-term. Morris water maze (MWM) and passive avoidance (PA) tests were used to determine learning and memory functions.

RESULTS: In the MWM test, there is a significant increase in the acquisition latency (1–4 days) of 24-month-old rats. There is a significant reduction in the “time spent in the escape platform’s quadrant” in 24-month-old rats compared to 4-month-old rats in the probe trial of the MWM test. YC-1 treatment reversed the reduction of the “time spent in the escape platform’s quadrant” of 24-month-old rats. In the PA test, there was no significant difference in the 1st-day latency of rats in all groups. On the 2nd day, retention latency significantly decreased in the 24-month-old rats compared to 4-month-olds. YC-1 reversed the diminished retention latency in 24-month-old rats. YC-1 treatment and aging did not affect results of the locomotor activity test or the foot-shock sensitivity test, suggesting our results were not due to a change in motor activity or disability of the animals.

CONCLUSIONS: Our findings suggest that activation of the NO-sGC-cGMP pathway plays an important role in spatial and emotional learning and memory functions in aged rats.

Keywords: Avoidance Learning - drug effects, Aging - physiology, Indazoles - pharmacology, Memory - drug effects, Motor Activity - drug effects, Reaction Time - drug effects