MODELING THE NICOTINIC RECEPTOR LOSS IN DEMENTIA USING THE NICOTINIC ANTAGONIST MECAMYLAMINE - EFFECTS ON HUMAN COGNITIVE-FUNCTIONING

The loss of central nicotinic receptors is a neurochemical hallmark of several degenerative brain disorders, notably Alzheimer's disease (AD ) and Parkinson's disease (PD). However, uncertainty has remained abou t the significance of this loss for the cognitive symptomatology of th ese disorders. Symptoms of impaired acquisition of information and sho rt-term storage, impaired memory consolidation, attention, visual perc eption, and speed may reflect nicotinic lesions. Administration of the nicotinic antagonist mecamylamine in young and elderly humans produce s significant dose-related impairment of new learning, liberalization of response bias, and slowing of reaction time. These results suggest that mecamylamine may in part model the results of nicotinic receptor loss in AD and that nicotinic augmentation of some aspects of cognitiv e functioning may be a worthwhile strategy to pursue, particularly if agents can be developed that are more selective than nicotine itself. (C) 1994 Wiley-Liss, Inc.