Spatial performance is severely impaired in rats with combined reduction of serotonergic and cholinergic transmission

A possible interaction between serotonergic and cholinergic neurotransmission was examined in relation to the performance of a spatial memory task. Blockade of cholinergic transmission with a high dose of atropine was sufficient to impair performance of a water maze task. A partial reduction of cholinergic transmission using a low dose of atropine had no effect on this performance. Reducing serotonin synthesis, using a specific inhibitor of tryptophane hydroxylase p-chlorophenylalanine (PCPA) also had no effect on performance of such a task. However, a combined treatment with a low dose of atropine and PCPA severely impaired the performance of rats in the water maze. The rats were impaired in both acquisition of the initial spatial task and in reacquisition of a new spatial position (= working memory). These findings suggest an interaction between cholinergic and serotonergic transmission in acquisition and retention of spatial information. Furthermore they propose that deficits in cognitive abilities, observed in aging or Alzheimer's disease, may result from the combined reduction in cholinergic and serotonergic transmission.