Administration of Cilostazol Mitigates Learning and Memory Disturbance in a Rat Model of Amnesia by Modifying Cholinergic Function and Neuroinflammation.

Scopolamine-induced amnesia is associated with impairment of the cholinergic system and disruption of oxidative balance. Evidence supports the therapeutic potential of cilostazol (Cil), a phosphodiesterase-3 inhibitor, in individuals with mild cognitive impairment. An amnesic rat model was induced using scopolamine. To investigate the neuroprotective mechanisms of Cil, oral treatment with Cil and donepezil (DNP, positive control) was administered over three weeks. Behavioral assessments were conducted between days 14 and 21, followed by analysis of neurochemical alterations in hippocampal tissue. Scopolamine impaired learning and memory. Cil and DNP reduced escape latency and path length in scopolamine-exposed rats (P = 0.03-P < 0.001). Treated rats also spent more time in the target quadrant during the Morris water maze test (P = 0.03 and P < 0.001). In the passive avoidance test, both agents decreased dark compartment entries and duration, while increasing latency to enter and time in the light compartment (P = 0.04-P < 0.001). Cil and DNP also attenuated oxidative stress by reducing lipid peroxidation and enhancing antioxidant markers, including sulfhydryl groups and superoxide dismutase (SOD) activity (P = 0.04-P < 0.001). Scopolamine increased hippocampal acetylcholinesterase (AChE) activity and upregulated TNF-α and IL-1β mRNA expression. Both were suppressed following treatment with Cil and DNP (P = 0.02-P < 0.001). Additionally, Cil and DNP elevated hippocampal levels of sulfhydryl groups (P = 0.01-P < 0.001), SOD activity (P = 0.01-P < 0.001), and CHRM1 mRNA expression (P = 0.002 and P < 0.001). Collectively, these results support a potential role for Cil in mitigating scopolamine-induced cognitive impairment by restoring redox homeostasis, modulating AChE activity, and suppressing neuroinflammation.