The most detailed picture yet of a key receptor in the brain that influences the effectiveness of serotonin-related antidepressants has been provided by researchers at University of Michigan. The finding paves the way for a more targeted treatment of depression and anxiety with fewer side effects.
Depressive disorders change a person's mood, emotions and physical well-being and can co-occur with anxiety disorders and substance abuse.
"There are big drawbacks in the current therapies for depression. Therapeutic benefits are delayed, there are unwanted side effects, and it's not unusual for depressive symptoms to return," said senior author Dr. John Traynor, professor of pharmacology at the U-M Medical School and director of the U-M Substance Abuse Research Center.
The best current treatments for depression are selective serotonin reuptake inhibitors, or SSRIs. These drugs work by flooding the brain's synapses with serotonin, a neurotransmitter linked with mood, and increasing signalling through the more than 20 serotonin receptors in the brain.
However the team of researchers showed that one particular pathway, the serotonin 5HT1a receptor is linked with antidepressive and anti-anxiety behaviour in mice.
"Rather than activating all serotonin receptors as SSRIs do, one could increase signaling through the one critical serotonin receptor that our research shows is important for anti-depressant behavior," said co-author Dr. Richard R. Neubig.
The study details the complex actions of a family of proteins, known as RGS proteins that act as brakes on neurotransmitter signaling.
Researchers created a mutant mouse to boost serotonin signalling at the 5HT1a receptor.
This was done by genetically inhibiting the activity of braking proteins.
Without the normal brake on serotonin signalling, these mutant mice showed antidepressive behaviour even without being given antidepressant drugs.
The mice were also more responsive to SSRIs.
According to the authors, further research could lead to drugs capable of inhibiting the RGS proteins and which would target the antidepressant signal where it is required on critical 5HT1a receptors.
The study appears in the journal Proceedings of the National Academy of Sciences.