Effects of tacrine (THA) on spatial reference memory and cholinergic enzymes in specific rat brain regions

Cognitive function of rats treated with saline (control), THA (8 mg/kg, i.p.), scopolamine (5 mg/kg, i.p.), or a combination of THA (8 mg/kg) and scopolamine (5 mg/kg) was tested in the Morris water maze. The latency to find the platform in the water maze was used to evaluate performance. THA did not significantly alter the latency period as compared to control rats. Scopolamine resulted in a highly significant (p<0.01) increase in latency period (183% increase) as compared to saline treated controls. However, when THA was concurrently administered with scopolamine, it was able to completely reverse the performance decrement induced by scopolamine. Immediately following spatial reference memory testing, animals were sacrificed by decapitation one hour post injection. Brains were immediately removed and the cortex, hippocampus, hypothalamus, and pituitary were dissected and their choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity were determined spectrophotometrically. THA administration resulted in a significant increase in ChAT activity in the cortex (23% increase). However, when THA was concurrently administered with scopolamine, a significant increase in ChAT activity was observed in cortex (77% increase), hippocampus (32% increase), hypothalamus (97% increase), and pituitary (92.5% increase). THA administration resulted in a significant decrease in AChE activity (p<0.001) in cortex (62% decrease), hippocampus (78% decrease), and hypothalamus (90% decrease). When tacrine was administered with scopolamine, a significant increase was found in the cortex (197% increase) and the hippocampus (207% increase). In conclusion, the increase in ChAT activity produced by tacrine may in part explain its ability to reverse the scopolamine induced decrease in spatial reference memory and may play a role in its beneficial effect in improving cognitive ability.