Development of nicotinic drug therapy for cognitive disorders.

Nicotine, as well as other nicotinic drugs, may provide useful therapeutic treatment for a variety of cognitive impairments including those found in Alzheimer's disease, schizophrenia and attention deficit hyperactivity disorder (ADHD). We have found that nicotine skin patches significantly improve attentional performance in people with these disease states as well as normal nonsmoking adults. Animal models are critical for determining the neurobehavioral bases for nicotinic effects on cognitive function. We have found in lesion and local infusion studies with rats that the hippocampus is an important substrate for nicotinic effects on working memory function. Both alpha7 and alpha4beta2 nicotinic receptors in the hippocampus are involved. Further work has investigated the relationship of nicotinic systems with dopaminergic and glutaminergic systems in the basis of cognitive function. Nicotine has proven to be a useful prototypic compound for the family of nicotinic compounds. It produces cognitive improvements in both animal models and clinical populations. Recent work with more selective nicotinic receptor agonists and antagonists in animal models is providing important information concerning the neural mechanisms for nicotinic involvement in cognitive function and opening avenues for development of safe and effective nicotinic treatments for clinical use.