Effects of pioglitazone injection into hippocampal CA1 area on spatial learning and memory deficits in rats

Pioglitazone from thiazolidinediones generation, represent a new antidiabetic drugs that have been introduced in the world recently. Thiazolidinediones can improve insulin resistance by activating the nuclear peroxoxisome proliferator activated receptor-γ (PPAR-γ) and increasing insulin sensitivity in their receptors. Insulin and its receptors are found in specific areas of CNS with a variety of region-specific functions. The effects of insulin in CNS are different from its direct glucose regulation in the periphery. Hippocampus and cerebral cortex distributed insulin/insulin receptor have been shown to be involved in brain cognitive functions. In the present study, the effect of pioglitazone microinjection into CA1 region of rat hippocampus using Morris water maze performance has been investigated. In this experimental study, male N-MRI rats were randomly divided into control, DMF (dimethyl formamide) and pioglitazone groups (0.001, 0.01, 0.1, 1, 10 µg/rat). Drugs were injected (1 µl/rat) into CA1 region bilaterly during 1 min. Thirty minutes after the intrahippocampal injection of drugs, water maze training was started. Pioglitazone had a dose dependent effect. The spatial learning and memory didn’t change with lower dose of pioglitazone, but improved with intermediate doses, while they impaired with higher dose. These results suggest that intrahippocampal injection of pioglitazone may have a dose-dependent effect on spatial learning and memory in rats in range of 0.001 to 1 µg/rat.