The modulatory neurotransmitters activate G protein-coupled receptors, which share signal transduction systems in cells. In addition to regulating key physiological functions, these systems are involved in human mental and neurological diseases. We are particularly interested in the histaminergic system, which interacts with other systems in regulation of, for instance, sleep, diurnal rhythms, feeding, and addiction. Plasticity of these systems is important but poorly understood in both normal and diseased brain.