A new twist on depression therapy could involve breaking up a pair of brain receptors for dopamine, a neurotransmitter implicated in the debilitating condition.
Brain cells sense dopamine via 5 different molecular receptors, D1-D5, and different receptors can cause distinct molecular changes in brain cells when they are activated. These sentinels typically work alone, but recent research has found that combinations of dopamine receptors can pair up and produce signals different from those of individual receptors.
Now, Fang Liu’s team at the University of Toronto in Canada found that the D1-D2 duo was present at higher levels in the autopsied striata (brain regions involved in reward) of depressed patients, compared to those of healthy people.
Her team then created a peptide that breaks up the D1-D2 tandem and injected it into the brains of mice. They faired better on two tests commonly used to measure depressive symptoms in mice, compared to rodents that didn’t receive the peptide. The work is published online today in Nature Medicine.
It’s unclear how the D1-D2 pair could promote depression, but Liu says the tandem appears to influence another protein, BDNF, that is linked to the condition.
And given the huge need for new antidepressants – at least a third of patients don’t respond to any drugs – Liu thinks it’s worth pursuing drugs that block dopamine receptor pairs. Her team is working on improving their peptide, as well as looking for small molecules that break up the dopamine receptor and which wouldn’t need to be injected into the brain.
Image of Prozac capsules courtesy of Wikimeda Commons