Neonatal neurosteroid levels are determinant in shaping adult prepulse inhibition response to hippocampal allopregnanolone in rats
Psychoneuroendocrinology. 2013-08-01; 38(8): 1397-1406
DOI: 10.1016/j.psyneuen.2012.12.007
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Darbra S(1), Modol L, Vallée M, Pallarès M.
Author information:
(1)Departament de Psicobiologia i Metodologia en Ciències de la Salut, Institut
de Neurociències, Universitat Autònoma de Barcelona, 08193 Cerdanyola del
Valles, Campus de Bellaterra, Barcelona, Spain.
Diverse studies indicate that the alteration of the physiological levels of
neurosteroids in early neonatal phases provokes alterations in the maturation of
certain cerebral structures. Allopregnanolone (ALLO) has important modulatory
effects in the hippocampus during the postnatal period where the adult pattern
of inhibitory transmission is being established. In order to study whether
endogenous neonatal ALLO levels would be a determinant parameter involved in
mediating adult hippocampal GABAA system maturation, we investigated the effects
of neonatal finasteride (50mg/kg, SC) treatment and ALLO (ALLO; 20mg/kg, SC)
supplementation on an animal behavioural model with relevance to
neurodevelopmental disorder, such as schizophrenia. Two sets of experiments were
conducted. Neonatal treatment (from postnatal day (pnd) 5 to pnd9) was performed
in 23 male Wistar rats and steroid quantification was performed in hippocampal
homogenates at pnd9. A second group (n=127) underwent neonatal treatment
(pnd5-pnd9) and were submitted to hippocampal surgery at 80d. The behavioural
response to bilateral intrahippocampal neurosteroid administration (ALLO,
0.2μg/0.5μl per side or pregnenolone sulphate 5ng/0.5μl per side) on
novelty-induced exploration activity and prepulse inhibition (PPI) was assessed
at 95d. Results showed that neonatal ALLO and finasteride administration
decreased novelty directed exploratory behaviour and impaired the prepulse
inhibition of the acoustic startle response at 95 days of age. Moreover,
intrahippocampal ALLO increased head-dipping behaviour independently of the
neonatal treatment, while intrahippocampal ALLO decreased PPI only in
finasteride and ALLO groups. The results obtained in the present study indicate
the importance of neonatal neurosteroid levels in the development of hippocampal
function and their relevance in a behavioural phenotype that some have likened
to that present in schizophrenia.
Copyright © 2012 Elsevier Ltd. All rights reserved.