His laboratory is currently investigating the molecular, cellular and biochemical properties of dopamine receptors and their role in neuronal signaling. The long-term goal of the Molecular Neuropharmacology Section is the characterization of neurotransmitter receptor-mediated information transduction, and its regulation, across neuronal membranes. The primary model systems under investigation are those receptors that are linked to their signal transduction pathways via guanine nucleotide binding regulatory (G) proteins with specific emphasis on dopamine receptor subtypes. Specific G proteins have been shown to link these receptors to the activation and inhibition of various nucleotide cyclases, phospholipases, and several ion channels. In order to characterize these receptors at the biochemical and molecular levels and study their regulation, there are several ongoing interrelated lines of research. Ongoing projects include investigating receptor structure/function/pharmacology relationships, receptor-effector coupling mechanisms, G protein and beta-arrestin interactions, and molecular mechanisms of receptor desensitization and intracellular trafficking. We are also interested in using high throughput screening approaches to develop novel ligands for modulating dopamine receptor expression and signaling. These efforts have led to the discovery of allosteric ligands, biased agonists, and best-in-class selective agonists and antagonists of the D1, D2 or D3 dopamine receptor subtypes. These compounds may prove useful as chemical probes as well as novel pharmacological therapies for treating numerous neurological and psychiatric disorders associated with aberrant dopaminergic signaling.