Early handling modulates outcome of neonatal dexamethasone exposure.
Synthetic glucocorticoids such as dexamethasone (DEX) are used to prevent or treat respiratory disorders in prematurely born infants. Besides the short-term benefit on lung development, numerous human and animal studies have reported adverse neurodevelopmental side effects. In contrast, maternal care is known to exert a positive influence on neurodevelopmental outcome in rodents. The aim of the current study was therefore to investigate whether neonatal handling (days 1-21), known to induce maternal care, might serve as an intervention strategy modulating the adverse effects of DEX treatment (days 1-3). For this purpose we have measured the outcome of these early-life manipulations on development as well as adult endocrine and behavioral phenotype of male rats. Maternal care was observed during the first week of life and indeed enhanced in response to handling. Eye opening was accelerated and body weight reduced in DEX-treated animals. In adulthood, we report that handling ameliorated impaired spatial learning observed in DEX treated non-handled animals in the T-maze. Additionally, handling reduced susceptibility to the impact of DEX treatment in the water maze. Although DEX treatment and handling both resulted in enhanced negative feedback of the stress-induced corticosterone response and both reduced startle reactivity, the acquisition of fear was only reduced by handling, without effect of DEX. Interestingly, handling had a beneficial effect on pre-pulse inhibition, which was diminished after DEX treatment. In conclusion, these findings indicate that handling of the neonate enhances maternal care and attenuates specific DEX-induced alterations in the adult behavioral phenotype.
Division of Medical Pharmacology, LACDR/LUMC, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands. s.e.f.claessens@gmail.com
Sanne E F
SE
Claessens
Nikolaos P
NP
Daskalakis
Melly S
MS
Oitzl
E Ronald
ER
de Kloet
D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003907:Dexamethasone / Q000009:adverse effects* / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005260:Female; D048788:Growth and Development / Q000187:drug effects* / Q000502:physiology; D006234:Handling, Psychological; D007266:Inhibition, Psychological; D008297:Male; D008425:Maternal Behavior / Q000502:physiology / Q000523:psychology*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology / Q000523:psychology; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D003907:Dexamethasone