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Alterations in neonatal neurosteroids affect exploration during adolescence and prepulse inhibition in adulthood.
- Source :
-
Psychoneuroendocrinology [Psychoneuroendocrinology] 2010 May; Vol. 35 (4), pp. 525-35. Date of Electronic Publication: 2009 Sep 22. - Publication Year :
- 2010
-
Abstract
- Allopregnanolone (AlloP) is a neurosteroid that plays an important role during neural development. Alterations of endogenous neonatal allopregnanolone levels alter the localisation and function of GABA neurons in the adult brain and affect behaviour in adulthood. We have carried out research into the effects of an increase (AlloP administration) or a decrease (administration of finasteride, inhibitor of the AlloP synthesis) of neonatal AlloP levels during the fifth to ninth postnatal days in male Wistar rats on the novelty exploration (Boissier test) at adolescent ages (40 and 60 days old), and on the prepulse inhibition achievement in adulthood (85 days). We also investigated the role of a GABA(A) modulator (midazolam, 1, 1.75 or 2.5mg/kg body weight) in the long-lasting behavioural changes in adulthood (85 days). Results indicate that neonatal finasteride decreases both novelty-exploration (head-dipping and locomotion) and anxiety-relevant scores (the distance travelled in and the number of entries into the central zone) at adolescent age, along with a reduction in body weight and general locomotion. Also, neonatal AlloP administration decreases prepulse inhibition in adulthood. Prepulse inhibition disruption was only partially reproduced decreasing the neonatal AlloP levels by means of finasteride administration. Although there was no interaction between neonatal neurosteroid manipulation and adult benzodiazepine treatments, the effects of midazolam were dose-dependent: the lowest dose of midazolam increased whereas the highest disrupted the expected progressive reduction of the startle response (and the consequent improvement of the PPI percentage) after the gradual increase in prepulse intensity. Reduced prepulse inhibition of startle provides evidence of deficient sensorimotor gating in several disorders, including schizophrenia. Alterations of AlloP levels during maturation could partly explain the inter-individual differences shown by adult subjects in response to novelty (exploration) and in the sensorimotor gating and prepulse inhibition. Also, abrupt changes in neonatal levels of AlloP could be related to a susceptibility to neurodevelopmental disorders.<br /> (Copyright 2009 Elsevier Ltd. All rights reserved.)
- Subjects :
- 5-alpha Reductase Inhibitors
Aging physiology
Aging psychology
Animals
Animals, Newborn
Anti-Anxiety Agents administration & dosage
Anti-Anxiety Agents pharmacology
Brain drug effects
Brain growth & development
Enzyme Inhibitors administration & dosage
Enzyme Inhibitors pharmacology
Female
Finasteride administration & dosage
Finasteride pharmacology
Male
Midazolam administration & dosage
Midazolam pharmacology
Neural Inhibition physiology
Neurotransmitter Agents metabolism
Pregnanolone administration & dosage
Pregnanolone pharmacology
Rats
Rats, Wistar
Reflex, Startle drug effects
Sexual Maturation physiology
Aging drug effects
Exploratory Behavior drug effects
Neural Inhibition drug effects
Neurotransmitter Agents pharmacology
Sexual Maturation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3360
- Volume :
- 35
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Psychoneuroendocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 19775818
- Full Text :
- https://doi.org/10.1016/j.psyneuen.2009.08.020