Low dose tetrahydroaminoacridine (THA) improves cognitive function but does not affect brain acetylcholine in rats

Eight days of treatment with two low doses of tetrahydroaminoacridine (THA), given once daily, substantially improved radial maze performance in two groups of rats which showed persistent deficits either after ibotenic acid lesions at the source of forebrain cholinergic projections, or after 28 weeks treatment with alcohol (20% v/v) in drinking water. However, in immature, aged or aged and alcohol-treated rats, acetylcholine content was not significantly affected in any of the brain areas measured, even though the treatment regime had proved behaviourally effective. Inhibition of brain acetylcholinesterase activity was only marginally increased by this treatment regime. Thus, if THA influences behaviour by enhancing cholinergic transmission, its effects do not appear to be related to its activity as a cholinesterase inhibitor, and alternative mechanisms of action should be investigated.