Psychopharmacology

, Volume 198, Issue 3, pp 413–420

Permanent improvement in deficient sensory inhibition in DBA/2 mice with increased perinatal choline

  • Karen E. Stevens
  • Catherine E. Adams
  • Joan Yonchek
  • Cindy Hickel
  • Jeffrey Danielson
  • Michael A. Kisley
Original Investigation

DOI: 10.1007/s00213-008-1170-3

Cite this article as:
Stevens, K.E., Adams, C.E., Yonchek, J. et al. Psychopharmacology (2008) 198: 413. doi:10.1007/s00213-008-1170-3

Abstract

Rationale

Schizophrenia patients and certain inbred mouse strains (i.e., DBA/2) show deficient sensory inhibition which has been linked to reduced numbers of hippocampal α7 nicotinic receptors and to underlying polymorphisms in the promoter region for the α7 gene. Increasing maternal dietary choline, a selective α7 agonist, during gestation has been shown to produce long-term changes in adult offspring behavior (i.e., improved learning and memory in rats).

Objectives

The objective of this study is to improve sensory inhibition in DBA/2 mice through maternal choline supplementation.

Materials and methods

DBA/2 dams were placed on normal (1.1 g/kg) or supplemented (5 g/kg) choline diet throughout gestation and lactation. Offspring were placed on normal diet at weaning and were assessed for sensory inhibition parameters at adulthood. Evoked EEG responses to identical paired auditory stimuli were compared. At the end of the study, the brains were collected for autoradiographic assessment of hippocampal levels of α-bungarotoxin binding to visualize α7 nicotinic receptors.

Results

Offspring mice which were choline supplemented during gestation showed significantly improved sensory inhibition compared to mice gestated on the normal choline diet. The improvement was produced by a significant reduction in the response to the second stimulus, demonstrating improved inhibition to that stimulus. There was a concurrent increase in α7 receptor numbers in both the CA1 and dentate gyrus regions of the hippocampus suggesting that this increase may be responsible for the improved inhibition.

Conclusions

These data show that gestational choline supplementation produces permanent improvement in a deficit associated with schizophrenia and may have implications for human prenatal nutrition.

Keywords

SchizophreniaAuditory gatingα7 nicotinic receptorsAutoradiographyα-bungarotoxinCholine supplementation

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Karen E. Stevens
    • 1
    • 2
  • Catherine E. Adams
    • 1
    • 2
  • Joan Yonchek
    • 2
  • Cindy Hickel
    • 2
  • Jeffrey Danielson
    • 2
  • Michael A. Kisley
    • 3
  1. 1.Medical ResearchVeterans Affairs Medical CenterDenverUSA
  2. 2.Department of Psychiatry MS 8344University of Colorado at Denver and Health Sciences CenterAuroraUSA
  3. 3.Department of PsychologyUniversity of Colorado at Colorado SpringsColorado SpringsUSA