Dopamine used for targeted therapy for neuropsychiatric disorders

Posted Sep 5, 2018 by Tim Sandle
New research shows how dopamine plays an influence with neuropsychiatric disorders. The focus is with how dopamine receptors create signal within cells. It is hoped the research will lead to better and more targeted treatments.
The Human Brain
Brain preserved in formaldehyde.
By Gaetan Lee (CC BY 2.0)
The research comes from Columbia University Vagelos College of Physicians and Surgeons. The research examined the dopamine D2 receptor (coded D2R). This functions as a key target with the treatment of psychiatric disorders like schizophrenia and neurological conditions, such as Parkinson's disease.
With the central nervous system, the dopamine receptors play an important part in an array of neural processes. These processes include motor control, learning and memory, plus feelings associated with reward.
Dopamine is an organic chemical of the catecholamine and phenethylamine families that plays several important roles in the brain and body. In the brain, dopamine functions as a neurotransmitter, which is a chemical released by neurons to send signals in order ls to other nerve cells.
In terms of treatment and the D2 receptor, current drugs serve to either block or activate these receptors to address a particular receptor that is deemed to be dysfunctional. The downside, is that these antipsychotic drugs can trigger adverse side effects, such as weight gain, involuntary movements, or lower levels of motivation.
The research offers a new solution. The scientists discovered that D2Rs transmit signals through two mechanisms, which are described as activating G proteins or by what are termed G-protein independent arrestin-signaling. The outcome of this means that it should be possible to maintain the therapeutic effects while avoiding negative side effects. This can be achieved via by G protein signaling pathway activation.
This was based on rodent studies. The mice had been genetically engineered to carry a mutated D2R that only facilitated the arrestin pathway. With these mice, the mutant dopamine receptor restored motor function as with the non-mutant form of the receptor. This indicated that arrestin recruitment can enhance motor function on its own.
According to lead researcher, Dr. Jonathan Javitch, in conversation with Laboratory Roots: “We asked whether these signaling pathways might also lead to different behavioral effects at the D2R, and whether this might provide a new approach to improved antipsychotic drugs with fewer side effects.”
The next steps will be to repeat the studies and to move onto human trials, if the results continue to be successful, especially with minimizing the adverse side effects experienced by patients taking the existing, less targeted medications.
The research has been published in the journal Molecular Psychiatry. The research is titled “Arrestin recruitment to dopamine D2 receptor mediates locomotion but not incentive motivation.”