NICOTINIC ACETYLCHOLINE INVOLVEMENT IN COGNITIVE FUNCTION IN ANIMALS

Nicotinic cholinergic systems are involved with several important aspe cts of cognitive function including attention, learning and memory. Ni cotinic cholinergic receptors are located in many regions of the brain , including areas important for cognitive function such as the hippoca mpus and frontal cortex. Nicotinic agonists have been found in rodent and non-human primate studies to improve performance on a variety of m emory tasks. In a complementary fashion, nicotinic antagonists such as mecamylamine impair working memory function. In humans, similar effec ts have been seen. Nicotinic agonist treatment can improve attention, learning and memory and nicotinic antagonist treatment can cause defic its. To define the neural substrates of nicotinic involvement in cogni tive function, three areas of investigation are underway. 1) Critical neuroanatomic loci for nicotinic effects are beginning to be determine d. The hippocampus, frontal cortex and midbrain dopaminergic nuclei ha ve been found to be important sites of action for nicotinic involvemen t in memory function. 2) Nicotinic receptor subtype involvement in cog nitive function is being studied. There has been considerable recent w ork identifying nicotinic receptor subunit conformation including alph a and beta subunits. Nicotinic receptor subtypes appear to be associat ed with different functional systems; however, much remains to be done to determine the precise role each subtype plays in terms of cognitiv e function. 3) Nicotinic interactions with other transmitter systems a re being assessed. Nicotine receptors interact In important ways with other systems to affect cognitive functioning, including muscarinic AC h, dopamine, norepinepherine, serotonin, glutamate, and other systems. Nicotinic function in clinical populations and potential for therapeu tics has been investigated for Alzheimer's disease, Parkinson's diseas e, schizophrenia and attention deficit/hyperactivity disorder. Areas w hich need to receive greater attention are the exact anatomical locati on and the specific receptor subtypes critically involved in nicotine' s effects. In addition, more work needs to be done to develop and dete rmine the efficacy and safety of novel nicotinic ligands for use in th e long-term treatment of human cognitive disorders.