Dysregulation of GPCR function in the brain underlies numerous neuropsychiatric disorders. This symposium provides insights from preclinical studies on the regional specificity of GPCR signaling in the brain and on signal transduction adaptations observed under pathological conditions. The speakers share latest findings on the precise role of Regulators of G protein signaling, allosteric regulation of receptor signaling, and complexes between G protein beta subunits and SNARE proteins, in disease-induced plasticity and monoamine receptor function. The panel will discuss potential therapeutic avenues targeting G protein signaling components for treatment of neuropsychiatric disorders such as pain, Parkinson’s disease and Alzheimer’s disease.