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 A lzheimer's disease, schizophrenia and attention deficit hyperactivity disor der (ADHD). We have found that nicotine skin patches significantly improve attentional performance in people with these disease states as well as norm al nonsmoking adults. Animal models are critical for determining the neurob ehavioral bases for nicotinic effects on cognitive function. We have found in lesion and local infusion studies with rats that the hippocampus is an i mportant substrate for nicotinic effects on working memory function. Both a lpha 7 and alpha 4 beta 2 nicotinic receptors in the hippocampus are involv ed. Further work has investigated the relationship of nicotinic systems wit h 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 mode ls and clinical populations. Recent work with more selective nicotinic rece ptor agonists and antagonists in animal models is providing important infor mation concerning the neural mechanisms for nicotinic involvement in cognit ive function and opening avenues for development of safe and effective nico tinic treatments for clinical use. (C) 2000 Elsevier Science B.V. All right s reserved.