Alpha2 adrenergic receptor blockade : A faster way to beat the blues?

“Depression is a devastating psychiatric illness that affects 15-20% of the population. A major handicap for the treatment of depression is that all currently available antidepressant drugs take several weeks to exert their beneficial effects. Recent evidence indicates that this delay in the effects of antidepressant drugs is paralleled by a slow onset of accompanying cellular changes. Amongst these slowly occurring cellular changes is the increase in new neuron formation (neurogenesis) in the hippocampus, a change that is required for the behavioral effects of antidepressants.  A major advance to the treatment of depression would be the development of rapid-action antidepressant treatments which speed up both, the neurogenic and behavioral effects of antidepressants. We have shown that the neurotransmitter norepinephrine regulates the birth of new neurons in the hippocampus. However, it works differently on two of it's receptors-decreasing stem cell turnover through the  alpha2-adrenergic receptor and increasing stem cell turnover through the b3 adrenergic receptor. We find that when the alpha-2 adrenergic receptor is blocked at the same time as giving an antidepressant drug, this acts to significantly speed up the neurogenic and behavioral effects of the antidepressant treatment. These studies underscore the importance of alpha-2 adrenergic receptor blockade in future drug development of faster-acting antidepressants.”