As one of the most important elements in our body, zinc plays a part in both the pathophysiology
of depression and the antidepressant response. Patients suffering from major depression show
significantly reduced zinc levels, which are normalized following successful antidepressant treatment.
Recent studies have shown the interaction between zinc, GPR39 and neuropeptides, including galanin
and neuropeptide Y (NPY). The zinc-sensing receptor GPR39 forms heterotrimers with 5-HT1A and
the galanin receptor GalR1 upon their co-expression in mammalian cells. The oligomerization of these
heterotrimers is regulated by the zinc concentration, and this may have an influence on depressive-like
behavior. The antidepressant-like effect of zinc is linked to elevated levels of brain-derived neurotrophic
factor (BDNF) in brain structures associated with emotion, such as the hippocampus and the
amygdala. BDNF regulates neuropeptides, including NPY, cholecystokinin (CCK), and substance P or
galanin, which are also implicated in mood disorders. This review focuses for the first time on the interaction
between zinc, the GPR39 zinc receptor, BDNF and selected neuropeptides in terms of depression
in order to determine its possible role in the neuropharmacology of that illness.