Prenatal exposure to betamethasone decreases anxiety in developing rats: hippocampal neuropeptide y as a target molecule.
Repeated antenatal administration of betamethasone is frequently used as a life-saving treatment in obstetrics. However, limited information is available about the outcome of this therapy in children. The initial prospective studies indicate that there are behavioral impairments in children exposed to repeated courses of prenatal betamethasone during the third trimester of pregnancy. In this study, pregnant rats received two betamethasone injections on day 15 of gestation. Using immunohistochemistry, the expression of a powerful anxiolytic molecule neuropeptide Y (NPY) was determined on postnatal day (PN) 20 in the hippocampus and basolateral amygdala (structures related to anxiety and fear) of the offspring. Prenatal betamethasone exposure induced significant increases in NPY expression in the hippocampus but not in the amygdala. Indeed, behavioral tests in the offspring, between PN20 and PN22 in the open field, on the horizontal bar, and in the elevated plus maze, indicated decreases in anxiety, without impairments in motor performance or total activity. Decreased body weight in betamethasone-exposed rats confirmed long-lasting effects of prenatal exposure. Thus, prenatal betamethasone treatment consistently increases hippocampal NPY, with decreases in anxiety-related behaviors and hippocampal role in anxiety in rats. Animal models may assist in differentiation between pathways of the desired main effect of the antenatal corticosteroid treatment and pathways of unwanted side effects. This differentiation can lead to specific therapeutic interventions directed against the side effects without eliminating the beneficial main effect of the corticosteroid treatment.
Velísek
Libor
L
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. velisek@aecom.yu.edu
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000517:prevention & control*; D001522:Behavior, Animal / Q000187:drug effects; D001623:Betamethasone; D001835:Body Weight / Q000187:drug effects; D004622:Embryo, Mammalian; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012153:Retention, Psychology / Q000187:drug effects; D012737:Sex Factors
D009478:Neuropeptide Y; D001623:Betamethasone