Molecular Pharmacology Laboratory

Co-Section Heads

Dr. Susan George
Dr. Brian O’Dowd

Research Objective

Both human and rodent brains are studied to determine if the G-protein-coupled receptors have a mediating effect on drug dependence and schizophrenia. Some of the research findings may lead to the development of a new generation of highly specific drugs to treat these disorders.

Summary of Activities

The G-protein-coupled receptor (GPCR) family represents the largest and most versatile group of cell surface receptors. CAMH scientists have made a number of important discoveries that have significant implications for understanding schizophrenia and substance abuse.

The discovery that D₁ and D₂ receptor co-activation triggers a novel calcium signal in the brain and provides a potential new target for designing medications to treat schizophrenia and drug addiction.

Other important research findings include the following:

• The discovery that dopamine receptor oligomers (a protein complex) undergo a strict quality control process before being sent to the cell surface. This ensures that the receptors are in the correct conformation.
• The development of a novel cell-based strategy to screen for drugs and examine the formation of GPCR oligomers in living cells. This strategy enables dynamic evaluation of the cellular trafficking of specific oligomers.
• The identification of more than 70 novel human genes encoding GPCRs. The discovery of GPCR genes broadens the scope of pharmacology.
• The determination that dopamine release in response to several abused drugs (cocaine, morphine, nicotine, alcohol, and tetrahydrocannabinol – the main psychoactive substance found in the Cannabis plant) was completely abolished by activating the κ opioid receptor.
• The discovery of apelin peptide, a neurotransmitter and the natural chemical that activates the apelin receptor, may lead to a better understanding of higher brain functions, such as learning, mood regulation, stress responses, and appetite. The widespread distribution of the apelin peptides and receptors indicates the importance of their role in brain function.

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