Neonatal dexamethasone on day 7 in rats causes behavioral alterations reflective of hippocampal, but not cerebellar, deficits.
Developmental glucocorticoid treatment in rats has been shown to cause body and brain weight decrements concurrent with behavioral alterations. Here, Sprague-Dawley rats were treated with the synthetic glucocorticoid, dexamethasone (DEX), on postnatal day (PND) 7 (1.5 mg/kg, sc, injected in the morning and afternoon). Behavioral assessments of negative geotaxis, locomotor activity (open field, maze exploration, residential running wheel, residential figure 8 maze), open-field activity response to amphetamine, acoustic startle, prepulse inhibition (PPI) of acoustic startle, juvenile play behavior, anxiety (emergence tests), motor coordination (rotarod performance), spatial learning (Morris water maze and food-reinforced complex maze), and operant performance (time estimation and response inhibition) were assessed in male rats. Body weight was decreased beginning at PND 43 until sacrifice on PND 127. Whole and regional brain weights were less, especially hippocampus, cerebellum, brainstem, and cortical remnant. Indications of delayed development were apparent; specifically, DEX-treated rats took significantly longer to turn on PND 8, but not PND 9, in the negative geotaxis test. DEX treatment induced deficits in the Morris water maze that were similar to hippocampal deficits. Open-field activity changes were inconsistent; however, DEX-treated rats were hyperactive during the dark period in running wheel tests. There were no indications of changes in reactivity or emotionality.
Ferguson
S A
SA
HFT-132, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA. sferguson@nctr.fda.gov
Paule
M G
MG
Holson
R R
RR
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D003624:Darkness; D003907:Dexamethasone / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008027:Light; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D003907:Dexamethasone; D000661:Amphetamine