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Neonatal neurosteroid levels are determinant in shaping adult prepulse inhibition response to hippocampal allopregnanolone in rats.
- Source :
-
Psychoneuroendocrinology [Psychoneuroendocrinology] 2013 Aug; Vol. 38 (8), pp. 1397-406. Date of Electronic Publication: 2013 Jan 05. - Publication Year :
- 2013
-
Abstract
- 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.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- 5-alpha Reductase Inhibitors pharmacology
Age Factors
Animals
Animals, Newborn
Exploratory Behavior drug effects
Exploratory Behavior physiology
Finasteride pharmacology
Hippocampus drug effects
Hippocampus metabolism
Male
Microinjections
Motor Activity drug effects
Neurotransmitter Agents metabolism
Pregnanolone administration & dosage
Pregnanolone metabolism
Pregnanolone pharmacology
Pregnenolone administration & dosage
Pregnenolone metabolism
Pregnenolone pharmacology
Rats
Reflex, Startle drug effects
Sensory Gating drug effects
Hippocampus physiology
Neurotransmitter Agents pharmacology
Pregnanolone physiology
Sensory Gating physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3360
- Volume :
- 38
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Psychoneuroendocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 23294582
- Full Text :
- https://doi.org/10.1016/j.psyneuen.2012.12.007