Journal article
Neonatal neurosteroid administration results in development-specific alterations in prepulse inhibition and locomotor activity: Neurosteroids alter prepulse inhibition and locomotor activity
Psychopharmacology, Vol.186(3), pp.334-342
06/2006
Handle:
https://hdl.handle.net/2376/105252
PMID: 16586090
Abstract
Early life exposure to stress and to GABAA receptor modulators have well-defined and persistent behavioral effects. A single neonatal injection of the GABAergic neurosteroid allopregnanolone (3α-hydroxy,5α-pregnane-20-one, 10 mg/kg, i.p.) alters the localization of prefrontal cortex (PFC) interneurons in adulthood. Such displacement could result in disinhibited behavior associated with impaired development of the mesocortical dopamine system.To determine if there is a critical window in which allopregnanolone levels may impact the development and mature function of the mesocorticolimbic circuitry.Behavioral measures, including prepulse inhibition (PPI) and total locomotor activity, after amphetamine exposure were assessed at postnatal day 20 (P20) (prepuberty), P40 (puberty), P60 (postpuberty), and P80 (adulthood) in animals previously exposed to allopregnanolone (10 mg/kg) on P2 and P5. PFC tyrosine hydroxylase immunoreactivity was stereologically measured.P2 administration of allopregnanolone resulted in an increased locomotor response to amphetamine (14, 28% on P20 and P80, respectively) and reduced PPI (28, 22% on P20 and P80, respectively) at P20 and P80, whereas allopregnanolone administration on P5 increased locomotor response to amphetamine (20%) and reduced PPI (37%) at P80. Clozapine (7.5 mg/kg) pretreatment reversed the PPI deficit in P2-exposed animals. The total length of tyrosine hydroxylase immunopositive fibers in PFC was not altered by neonatal neurosteroid exposure, but more fibers were located in layers V/VI vs I–III.Altering neonatal allopregnanolone levels disrupts PFC-dependent behavior, indicating that allopregnanolone might be important for normal PFC circuitry development. The temporal exposure differences (P2 vs P5) and ontological-dependent effects (P20 and P80, but not P40 or P60) suggest critical windows of vulnerability to neurosteroid insult across development.
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Details
- Title
- Neonatal neurosteroid administration results in development-specific alterations in prepulse inhibition and locomotor activity
- Creators
- Samantha Gizerian - Department of Biomedical Sciences Charles R. Drew University of Medicine and Science 1731 S. 120th St Los Angeles CA 90059 USASheryl Moy - Curriculum in Neurobiology and Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill NC 27599 USAJeffrey Lieberman - Chair of Department of Psychiatry Columbia University & Director of New York State Psychiatric Institute 1051 Riverside Dr., Unit 04 New York NY 10032 USAA Grobin - Department of Psychiatry, UNC at Chapel Hill, CB #7160 7023 Neurosciences Hospital Chapel Hill NC 27599 USA
- Publication Details
- Psychopharmacology, Vol.186(3), pp.334-342
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Springer-Verlag; Berlin/Heidelberg
- Identifiers
- 99900546782101842
- Language
- English
- Resource Type
- Journal article