title: Neonatal finasteride administration alters hippocampal α4 and δ GABAAR subunits expression and behavioural responses to progesterone in adult rats.
abstract: 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.
authors.affiliation: Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Modol
authors.affiliation: 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.
authors.forename: Caty
authors.initials: C
authors.lastname: Casas
authors.affiliation: 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.
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
authors.affiliation: Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Llidó
authors.affiliation: Institut National de la Santé et de la Recherche Medicale (INSERM), Unité 862, Bordeaux, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Vallée
authors.affiliation: Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Pallarès
authors.affiliation: Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Sònia
authors.initials: S
authors.lastname: Darbra
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D018120:Finasteride / Q000494:pharmacology* / Q000633:toxicity; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D021122:Protein Subunits / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000096:biosynthesis*
chemical_list: C546262:Gabra4 protein, rat; D021122:Protein Subunits; D011963:Receptors, GABA-A; D011374:Progesterone; D018120:Finasteride