Neuromodulation is a fundamental physiological phenomenon underlying behavioral plasticity. Using a comprehensive research program that employs cellular, molecular, genetic, chemical, pharmacological and behavioral approaches, our goal is to explore the cellular and biochemical nature of neuromodulatory processes that are crucial for learning and memory, and behavioral adaptations to drugs of abuse. Neuromodulators such as dopamine, serotonin and norepinephrine exert pleiotropic effects in all animals. For example, dopamine plays a role in emotion, cognition and motor system in humans. These modulators function by binding to cell surface receptors to trigger intracellular biochemical changes. These changes, in turn, modify cellular output to generate behavioral responses. The beauty of the biological system is that there are multiple receptors for each modulator, and they are present in distinct brain areas, presumably to execute discrete physiological processes. One of the tantalizing key questions is: does one receptor carry out one or multiple functions? If it does multiple jobs, how does it control specificity? To tackle these issues, we are focusing on two modulators, dopamine and octopamine (functionally similar to norepinephrine of mammals) by employing Drosophila melanogaster as an animal model.