The function of the glutamate–nitric oxide–cGMP pathway in brain in vivo and learning ability decrease in parallel in mature compared with young rats

Aging is associated with cognitive impairment, but the underlying mechanisms remain unclear. We have recently reported that the ability of rats to learn a Y-maze conditional discrimination task depends on the function of the glutamate-nitric oxide-cGMP pathway in brain. The aims of the present work were to assess whether the ability of rats to learn this task decreases with age and whether this reduction is associated with a decreased function of the glutamate-nitric oxide-cGMP pathway in brain in vivo, as analyzed by microdialysis in freely moving rats. We show that 7-mo-old rats need significantly more (192 +/- 64%) trials than do 3-mo-old rats to learn the Y-maze task. Moreover, the function of the glutamate-nitric oxide-cGMP pathway is reduced by 60 +/- 23% in 7-mo-old rats compared with 3-mo-old rats. The results reported support the idea that the reduction in the ability to learn the Y-maze task (and likely other types of learning) of mature compared with young rats would be a consequence of reduced function of the glutamate-nitric oxide-cGMP pathway.