Effect of intrahippocampal CA1 injection of insulin on spatial learning and memory deficits in diabetic rats

Background: Diabetes mellitus is one of the most important diseases in all over the world. Insulin and its receptor are found in specific area of CNS with a variety of regions-specific functions different from its role in direct glucose regulation in the periphery. The hippocampus and cerebral cortex distributed insulin and insulin receptor has been shown to be involved in brain cognitive functions. Previous studies about the effect of insulin on memory in diabetes are controversial and further investigation is necessary.

Methods: Seventy male NMRI rats (250-300 g) were randomly divided into control, diabetic, saline-saline, saline-insulin (12, 18 or 24 mU), diabetic-saline, diabetic-insulin (12, 18 or 24 mU) groups. Diabetes was induced by streptozotocin (65 mg/kg, ip). Saline or insulin were injected bilaterally (1 µl/rat) into CA1 region of hippocampus during 1 min. Thirty minutes later, water maze training was performed.

Results: Insulin had a dose dependent effect. The spatial learning and memory were impaired with diabetes, and improved by insulin. Escape latency and swimming distance in a water maze in insulin treated animals were significantly lower (P<0.05) than control and diabetic groups. Percentage of time spent by animals in a target quarter in probe trial session showed a significant difference among groups. This difference was significant between insulin treated and the other groups (P<0.05).

Conclusions: Our findings suggest that injection of insulin into hippocampal CA1 area may have a dose-dependent effect on spatial learning and memory in diabetic rats.