[Effect of idebenone on scopolamine-induced impairment of short-term memory in rats]

The effects of a novel compound, idebenone [6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone] and cholinergic drug on short-term memory (STM) were studied in a delayed alternation task in rats. Rats were initially trained using a delayed alternation task in which a forced run to one arm of a T-maze was followed by a free-choice run. A correct free-choice response was defined as a turn toward the arm opposite to that in the forced run, and was rewarded with food pellets. When the time interval between the forced run and free-choice run was longer than 60 sec, the correct responses decreased by about 30% compared with that in no delay trials. After repeated training of the 60 sec-delayed alternation task, the effect of an anticholinergic drug scopolamine (0.1-0.5 mg/kg, ip) on the delayed alternation task was tested. The drug administered 20 min before the test significantly decreased the correct responses in a dose dependent manner. The effect of scopolamine (0.2 mg/kg, ip) was antagonized by the simultaneous administration of physostigmine (0.05-0.2 mg/kg, ip) in a dose dependent manner. Furthermore, physostigmine (0.1 and 0.2 mg/kg, ip) alone increased correct responses in the same task. Idebenone (3-30 mg/kg, ip), administered simultaneously with scopolamine, significantly improved the scopolamine-induced decrement of correct responses, with the highest efficacy at 10 mg/kg. The compound alone did not affect the number of correct responses. These results suggest that STM is closely related to the cholinergic system, and that idebenone may have an improving effect on the impairment of STM induced by a decreased cholinergic activity.