Idebenone improves learning and memory impairment induced by cholinergic or serotonergic dysfunction in rats.

The effects of idebenone, a cerebral metabolic enhancer, on learning and memory impairment in two rat models with central cholinergic or serotonergic dysfunction were investigated using positively reinforced learning tasks. A delayed alternation task using a T maze was employed to test the effect of idebenone on short-term memory impairment induced by a cholinergic antagonist, scopolamine. A correct response, defined as a turn toward the arm opposite to that in the forced run, was rewarded with food pellets. Scopolamine (0.2 and 0.5 mg/kg, i.p.) significantly decreased the correct responses to the chance level in the 60-s-delayed alternation task. The scopolamine (0.2 mg/kg, i.p.)-induced impairment of short-term memory was improved by idebenone (3-30 mg/kg, i.p.) or an acetylcholinesterase inhibitor, physostigmine (0.1 and 0.2 mg/kg, i.p.), administered simultaneously. The central serotonergic dysfunction model was produced by giving rats a diet deficient in tryptophan, a precursor of serotonin. The rats fed on a tryptophan-deficient diet (TDD) showed a slower learning process in the operant brightness discrimination task (mult V115 EXT) than did rats fed on a normal diet. Idebenone (60 mg/kg/day) admixed with the TDD decreased the number of lever-pressing responses emitted during the extinction periods. The percentage of correct responses was significantly higher in the idebenone-treated group than in the control TDD group. These results suggest that idebenone may improve both the impairment of short-term memory induced by a decreased cholinergic activity and the retardation of discrimination learning induced by central serotonergic dysfunction.