Behavioral Effects of Neurotrophins in Models of Stress and Depression

Summary : Irwin Lucki, Ph.D. will use an animal model to study the neurotrophins brain derived neurotrophic factor (BDNF) and insulin growth factor (IGF 1) as targets for novel effective antidepressant treatments. Neurotrophins and their receptors are good targets for the development of novel antidepressant drugs because they support neuronal growth and plasticity and can counteract the neurodegenerative effects of stress. BDNF is critical for survival and guidance of neurons during development, as well as for the survival and function of neurons in the adult brain. Dr. Lucki will examine the effects of BDNF and IGF 1, focusing on the identification of behavioral outcomes relevant for depression and other psychiatric disorders. In a prior study, Dr. Lucki was the first to report that these neurotrophins have long term effects and distinguished themselves from conventional antidepressant drugs. He believes these novel demonstrations will serve as models for the development of a comprehensive examination of the neuropharmacology of neurotrophins and behavior, enabling him to determine if low dose administration into specific areas of the forebrain are uniquely responsible for their long term behavioral effects, as well as enabling him to study specific receptors and signaling pathways to understand the physiological mechanisms which govern the behavioral actions of the neurotrophins. He will also develop a method which allows investigators to follow proposed reciprocal changes in neurotrophin levels produced by stress and antidepressant drug treatment. Current measures are unsatisfactory for dynamically measuring the concentrations of neurotrophins free to act on receptor targets. The development of this new method will significantly impact a new line of investigation that will be capable of measuring the impact of neurotrophins directly in different regions of the brain.