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.
Husum
Henriette
H
Institution of Clinical Neuroscience and Institution of Physiology and Pharmacology, Division of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Mathé
Aleksander A
AA
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005260:Female; D018020:Lithium Compounds / Q000494:pharmacology*; D008297:Male; D008426:Maternal Deprivation; D009478:Neuropeptide Y / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism*; D013431:Sulfates / Q000494:pharmacology*
D018020:Lithium Compounds; D009478:Neuropeptide Y; D013431:Sulfates; D003346:Corticotropin-Releasing Hormone; C054097:lithium sulfate; D003345:Corticosterone