Chronic administration of acetylcholinesterase inhibitor in the senescent rat brain

The effects of chronic administration of ENA-713, an acetylcholinesterase (AChE) inhibitor, on pre- and postsynaptic cholinergic indices were examined in the senescent rat brain. In the senescent group, the acetylcholine (ACh) level was markedly reduced in the frontal cortex, hippocampus, striatum and thalamus+midbrain, but these reductions were completely prevented by ENA-713. Moreover, although choline acetyltransferase (ChAT) activity was also significantly decreased in these four regions, it recovered in the frontal cortex, hippocampus and thalamus+midbrain after ENA-713 treatment. In contrast, cholinesterase (ChE) activity was not changed in any experimental groups. The maximum number (Bmax) of muscarinic M1 receptor (M1-R) binding site in the frontal cortex in the senescent group was decreased without any change in affinity, but this decrease was also inhibited by ENA-713. Thus, these findings suggest that ENA-713 may have protective, neurotrophic and therapeutic effects on aging-induced cholinergic dysfunction and be useful for the treatment of aging-related dementia, such as the Alzheimer-type dementia.