Alteration of neonatal Allopregnanolone levels affects exploration, anxiety, aversive learning and adult behavioural response to intrahippocampal neurosteroids
Behavioural Brain Research. 2013-03-01; 241: 96-104
DOI: 10.1016/j.bbr.2012.11.043
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Mòdol L(1), Darbra S, Vallèe M, Pallarès M.
Author information:
(1)Departament de Psicobiologia i Metodologia en Ciències de la Salut, Institut
de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra,
Barcelona, Spain.
Neurosteroids (NS) are well known to exert modulatory effects on ionotropic
receptors. Recent findings indicate that NS could also act as important factors
during development. In this sense, neonatal modifications of Allopregnanolone
(Allop) levels during critical periods have been demonstrate to alter the
morphology of the hippocampus but also other brain structures. The aim of the
present work is to screen whether the alterations of Allop levels modify adult
CA1 hippocampal response to NS administration. For this purpose, pups were
injected with Allop (20 mg/kg s.c.), Finasteride (5α-reductase inhibitor that
impedes Allop synthesis) (50 mg/kg s.c.) or Vehicle from postnatal day 5 (P5) to
postnatal day 9 (P9). NS levels were tested at P5. To test the behavioural
hippocampal response to NS in adulthood, animals were implanted with a bilateral
cannula into the CA1 hippocampus at 80 days old and injected with Allop (0.2
μg/0.5 μl), Pregnenolone sulphate (5 ng/0.5 μl) or Vehicle in each hippocampus.
After injections animals were tested in the Boisser test to assess exploratory
behaviour, the elevated plus maze to assess anxiety and the passive avoidance to
test aversive learning. Results indicate that alteration of neonatal Allop or
pregnenolone levels (by Allop and Finasteride administration, respectively)
suppressed intrahippocampal Allop anxiolytic effect in the EPM. Moreover our
results also indicate that manipulation of neonatal Allop levels (Allop and
Finast administration) alters exploratory and anxiety-like behaviour and impairs
aversive learning in the adulthood. These data point out the role of Allop in
the maturation of hippocampal function and behaviour.
Copyright © 2012. Published by Elsevier B.V.
DOI: 10.1016/j.bbr.2012.11.043
PMID: 23228522 [Indexed for MEDLINE]