EFFECT OF 4-(o-BENZYLPHENOXY)-N-METHYLBUTYLAMINE HYDROCHLORIDE (MCI-2016) ON THE SCOPOLAMINE-INDUCED DEFICIT OF SPONTANEOUS ALTERNATION BEHAVIOR IN RATS

抄録

To predict the possible activity on memory disorders, the effect of MCI-2016 was compared with those of physostigmine, choline chloride, methamphetamine, apomorphine, imipramine and calcium hopantenate by applying scopolamine-induced deficit of spontaneous alternation behavior (scopolamine-SA) as a proposed animal model for senile dementia. MCI-2016 was shown to improve the scopolamine-SA at doses of 25 to 100 mg/kg p.o. without producing any remarkable behavioral abnormalities. As for the effect of reference drugs, two types of cholinomimetic drugs (physostigmine and choline chloride) and methamphetamine were shown to be active. In the cases of physostigmine and methamphetamine, however, behavioral abnormalities were observed at those dose levels effective on scopolamine-SA. MIC-2016 potentiated the effect of physostigmine on scopolamine SA at non active doses of 10 to 20 mg/kg p.o. In comparison with the deleterious effect of scopolamine on spontaneous alternation (SA) behavior itself, none of the test drugs except for imipramine were shown to disrupt the SA. Considering the disruptive or improving actions of various agents on SA or scopolamine-SA, it may be suggested that the present model is relatively sensitive to those drugs which affect the cholinergic mechanism either directly or indirectly. Mechanisms of the actions of MCI-2016 and methamphetamine were also discussed with reference to possible involvement of cholinergic mechanisms.