Head: Raul R. Gainetdinov
Monoamines dopamine, serotonin and norepinephrine are important neurotransmitters in the CNS that regulate various aspects of complex behaviours and motor activity. Brain disorders, such as depression, schizophrenia, bipolar disorder, Parkinson’s Disease and attention deficit hyperactivity disorder (ADHD) have been primarily related to the dysregulation of monoaminergic pathways, but the underlying mechanisms of these multi-transmitter dysfunctions remain elusive. Many drugs clinically used in the management of these neuropsychiatric disorders, such as antipsychotics, psychostimulants and antidepressants, primarily act on monoaminergic neurotransmission.
Our laboratory uses a variety of techniques including genetic animal models, cellular systems, biochemical and molecular approaches to understand the pharmacology and role of monoamines and their receptors in health and disease. Investigations performed in mice with genetically enhanced or reduced monoaminergic transmission will be discussed. Particularly, we are using several genetic animal models of aberrant monoaminergic transmission generated by targeting plasma membrane transporters (DAT, NET), key synthesizing enzymes (TPH2), monoamine receptors, signal transduction and GPCR regulatory mechanisms (arrestins, GRKs).
We are also investigating the role of trace amines and their receptors (TAARs) in neuronal functions. These studies are eventually aimed to understand the molecular mechanisms involved in the manifestation of aberrant behaviors and responses to drugs that could be helpful to identify novel targets for pharmacological treatments of neuropsychiatric disorders.
Major lines of research:
Premont RT and Gainetdinov RR. Physiological roles of G protein-coupled receptor kinases and arrestins. Annual Rev Physiol (2007) 69: 511-534.
Beaulieu JM and Gainetdinov RR. The Physiology, Signaling and Pharmacology of Dopamine Receptors. Pharmacological Reviews (2011) 63: 182-217.
Dopamine Transporter Knock-out mice
Mice without dopamine can not move – model of Parkinson’s Disease
The joint SPBU Laboratory of Neuroscience and Molecular Pharmacology was funded by: