Classical conditioning of the rabbit's nictitating membrane response is a function of the duration of dietary cholesterol.

Modifying dietary cholesterol may improve learning and memory but very high cholesterol can cause pathophysiology and death. Rabbits fed 2% cholesterol for 8, 10 or 12 weeks with 0.12 ppm copper added to distilled water and rabbits fed a normal diet without copper added to distilled water (0 weeks) were given a difficult trace classical conditioning task and an easy delay conditioning task pairing tone with corneal air puff. The majority of cholesterol-fed rabbits survived the deleterious effects of the diet but survival was an inverse function of the diet duration. Compared to controls, the level of classical conditioning and conditioning-specific reflex modification were an inverted "U"-shaped function of diet duration. Highest levels of responding occurred in rabbits on cholesterol for 10 weeks and trace conditioning was negatively correlated with the number of hippocampal beta-amyloid-positive neurons. Rabbits on the diet for 12 weeks responded at levels comparable to controls. The data provide support for the idea that dietary cholesterol may facilitate learning and memory but there is an eventual trade off with pathophysiological consequences of the diet.