Neonatal finasteride administration alters hippocampal α4 and δ GABAA R subunits expression and behavioural responses to progesterone in adult rats
Int. J. Neuropsychopharm.. 2013-09-09; 17(02): 259-273
DOI: 10.1017/S1461145713000989
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Modol L(1), Casas C(2), Navarro X(2), Llidó A(1), Vallée M(3), Pallarès M(1), Darbra S(1).
Author information:
(1)Departament de Psicobiologia i Metodologia de les Ciències de la Salut,
Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra,
Barcelona, Spain.
(2)Department of Cell Biology, Physiology and Immunology, Institut de
Neurociències, Universitat Autònoma de Barcelona, and Centro de Investigación
Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 08193
Bellaterra, Barcelona, Spain.
(3)Institut National de la Santé et de la Recherche Medicale (INSERM), Unité
862, Bordeaux, France.
Allopregnanolone is a neurosteroid that has been reported to fluctuate during
early developmental stages. Previous experiments reported the importance of
neonatal endogenous allopregnanolone levels for the maturation of the central
nervous system and particularly for the hippocampus. Changes in neonatal
allopregnanolone levels have been related to altered adult behaviour and with
psychopathological susceptibility, including anxiety disorders, schizophrenia
and drug abuse. However, the mechanism underlying these changes remains to be
elucidated. In the present study we assessed changes in hippocampal expression
of α4 and δ GABAA receptor (GABAAR) subunits as a consequence of neonatal
finasteride (a 5-α reductase inhibitor) administration during early development
(PD6 to PD15) in male rats. We observed that the treatment altered the temporal
window of the natural peak in the expression of these subunits during
development. Additionally, the level of these subunits were higher than in
non-handled and control animals in the adult hippocampus. We observed that in
adulthood, neonatal finasteride-treated animals presented an anxiogenic-like
profile in response to progesterone administration which was absent in the rest
of the groups. In conclusion, these results corroborate the relevance of
neonatal maintenance of neurosteroid levels for behavioural anxiety responses in
the adult, and point to some of the mechanisms involved in this alterations.
DOI: 10.1017/S1461145713000989
PMID: 24011224 [Indexed for MEDLINE]