Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes.

Experiences of early life stress are more prevalent among depressed patients than healthy controls. Neuropeptide Y (NPY) was suggested to play a role in the pathophysiology of depression. Consequently, we investigated in adult rats the effects of maternal deprivation for 3 h/day during postnatal days (PND) 2-14 and of dietary lithium during PND 50-83 on brain levels of NPY-like immunoreactivity (LI). Brain levels of corticotropin-releasing hormone (CRH) and serum corticosterone were also measured. Maternal deprivation reduced NPY-LI levels in the hippocampus and the striatum but increased NPY-LI and CRH-LI levels in the hypothalamus. Lithium treatment counteracted the effect of maternal deprivation in the hippocampus and striatum by increasing NPY-LI levels. In the hypothalamus, lithium tended to decrease CRH-LI but further increased levels of NPY-LI; it also increased serum corticosterone levels. The results suggest that early life stress has long-term effects on brain NPY with implications for the development of depression/vulnerability to stress, and that one therapeutic mechanism of action of lithium is to increase brain NPY.