Dr. Wecker's general interests are to understand how brain chemistry affects or determines behaviors with an emphasis on the etiology and treatment of neuropsychiatric and neuromotor disorders. Multidisciplinary approaches are used to elucidate how age, drugs of abuse, and environmental and genetic factors affect both brain chemistry and behavior. A major emphasis has focused on cholinergic mechanisms in the brain, particularly on the role and regulation of nicotinic receptors. Early studies demonstrated that sustained supplementation of rats with choline supports the synthesis of acetylcholine during conditions of increased neuronal demand and increases the density of neuronal nicotinic receptors in the brain. Since that time studies have focused on characterizing the regulation of alpha4beta2 nicotinic receptors and have demonstrated that these receptors are regulated by phosphorylation/dephosphorylation mechanisms that alter receptor formation, maturation and expression, and that sustained nicotinic receptor activation modifies these events. Current studies are investigating the role of neuronal nicotinic receptors in ataxia, and mechanisms mediating the neurotrophic actions of nicotinic agonists. Concurrent investigations are elucidating the role of these receptors in mediating both nicotine and alcohol addiction, and how perturbations in receptor expression during adolescence can predispose the adult brain to drug-seeking behavior. Results from these studies will further our understanding of the role and regulation of these receptors in neuropsychiatric and neuromotor disorders, and may lead to new strategies for the treatment of these disorders.