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Nakamura K, Kurasawa M CNS Supporting
Laboratory, Nippon Roche Research Center, 200 Kajiwara, Kamakura,
247-8530, Kanagawa, Japan.
kazuo.nakmura@roche.com The anxiolytic effects
of aniracetam have not been proven in animals despite its clinical
usefulness for post-stroke anxiety. This study, therefore, aimed to
characterize the anxiolytic effects of aniracetam in different
anxiety models using mice and to examine the mode of action. In a
social interaction test in which all classes (serotonergic,
cholinergic and dopaminergic) of compounds were effective,
aniracetam (10-100 mg/kg) increased total social interaction scores
(time and frequency), and the increase in the total social
interaction time mainly reflected an increase in trunk sniffing and
following. The anxiolytic effects were completely blocked by
haloperidol and nearly completely by mecamylamine or ketanserin,
suggesting an involvement of nicotinic acetylcholine, 5-HT2A and
dopamine D2 receptors in the anxiolytic mechanism. Aniracetam also
showed anti-anxiety effects in two other anxiety models (elevated
plus-maze and conditioned fear stress tests), whereas diazepam as a
positive control was anxiolytic only in the elevated plus-maze and
social interaction tests. The anxiolytic effects of aniracetam in
each model were mimicked by different metabolites (i.e., p-anisic
acid in the elevated plus-maze test) or specific combinations of
metabolites. These results indicate that aniracetam possesses a wide
range of anxiolytic properties, which may be mediated by an
interaction between cholinergic, dopaminergic and serotonergic
systems. Thus, our findings suggest the potential usefulness of
aniracetam against various types of anxiety-related disorders and
social failure/impairments.
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