THE 5-HT1A ANTAGONIST, WAY-100635, AMELIORATES THE COGNITIVE IMPAIRMENT INDUCED BY FORNIX TRANSECTION IN THE MARMOSET

Fornix transection in the marmoset produces a specific pattern of cogn itive deficits, notably a lack of ability to recall visuospatial tasks learnt preoperatively, and a deficit in acquiring new visuospatial ta sks following transection. Previous work has shown that this learning impairment can be ameliorated by cholinergic agonists, suggesting that it occurs as a consequence of destroying the cholinergic projection f rom the vertical limb of the diagonal band to the hippocampus which ru ns through the fornix. We have now shown that this deficit in new lear ning can be significantly alleviated by the 5-HT1A antagonist, WAY 100 635. This result supports the suggestion that 5-HT1A projections are i nhibitory on the same target cells for which cholinergic projections a re excitatory, and that loss of function in the target cells caused by loss of excitatory tone can be compensated by blockade of inhibitory tone. Since cholinergic loss in the hippocampus (and neocortex) occurs in association with cognitive decline in Alzheimer's disease, these r esults suggest that 5-HT1A antagonists may have a role in the treatmen t of some of the cognitive symptoms of dementia.