The overall focus of the Division of Neurochemistry encompasses multifaceted aspects of the biology of neuropsychiatric and drug addiction disorders. The research is multidisciplinary, highly collaborative, and utilizes biochemical, molecular, cellular, behavioral and genetic approaches. Support is primarily provided through NIH research grants. The Division is currently staffed by three post-doctoral fellows, five research assistants, and a half-time administrative assistant. The research program is integrated with and makes use of the facilities, personnel and resources of several Divisions at the New England Primate Research Center. These range from collaborative projects with the Divisions of Behavioral Biology, Microbiology and Comparative Pathology, to significant use of Core services including confocal microscopy, cell sorting, DNA sequencing, blood sampling and necropsy services, and extensive use a our newly established Primate Genetics Core.

An overarching aim of the research is to model human genetic variance underlying polygenic neuropsychiatric diseases, drug addiction susceptibility and alcoholism in rhesus macaques. Our working hypothesis is that genetic variation in key genes implicated in these disorders in humans are functionally mimicked by comparable, but not necessarily identical, alleles present in rhesus monkeys. Though rhesus monkeys often harbor different alleles than occur in humans, genetic variants in this species nevertheless have shown common functionality compared with polymorphisms in orthologous human genes. The Division's research program aims to systematically uncover these naturally-occurring, functionally comparable polymorphisms in the rhesus macaque. Our approach is to identify, catalog, and functionally assess the rhesus monkey genetic variants while correlating alleles with directly observable and measurable phenotypic and physiological traits. Our polymorphism discovery platform and our ongoing in vitro functional assessment strategies synergize into an expanding data matrix that forms the necessary basis for developing rhesus macaque cohorts that genetically and phenotypically emulate human populations with increased vulnerability to specific neuropsychiatric and addiction disorders. It is our long-term ambition to identify and utilize distinct rhesus monkey cohorts to elucidate the genetic interactions influencing disorder-related phenotypes and as a preclinical platform for the development of pharmacogenomic-informed human personalized medicine.

The theme of developing novel therapeutics for neuropsychiatric and substance abuse disorders carries through to a second research program focused on the neurobiology of neuropsychiatric and substance abuse disorders. Our current emphasis involves cloning, assessing pharmacology and determining receptor distribution of Trace Amine-Associated Receptors. "Trace amines", monoamines that are structurally-related to dopamine, norepinephrine and serotonin but that exist in brain only at trace levels, have been known for over 30 years and have long been implicated in substance abuse, depression, ADHD, eating disorders, schizophrenia, and other neuropsychiatric diseases. Trace Amine-Associated Receptor 1 (TAAR1), cloned from rhesus monkey in our lab, is a primary target of common and uncommon endogenous monoamines, as well as amphetamines. We have shown that TAAR1 and monoamine autoreceptors co-modulate monoamine transporters and that TAAR1 mediates methamphetamine-induced effects on monoamine transporter function, revealing a novel mechanism for monoamine transporter regulation and methamphetamine action in brain. Our studies of TAAR1 in brain monoaminergic systems suggest that the receptor is a plausible target for the development of novel therapeutics for neuropsychiatric disorders and particularly, methamphetamine addiction.