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Neuropsychopharmacology. 2002 Nov;27(5):756-64.

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

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  • 1Institution of Clinical Neuroscience and Institution of Physiology and Pharmacology, Division of Pharmacology, Karolinska Institutet, Stockholm, Sweden.


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.

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