Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia

Biol Psychiatry. 2006 Sep 15;60(6):591-6. doi: 10.1016/j.biopsych.2006.02.033. Epub 2006 May 12.

Abstract

Background: Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats.

Methods: Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801.

Results: DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response.

Conclusions: These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / methods
  • Animals
  • Antipsychotic Agents / pharmacology
  • Behavior, Animal / drug effects
  • Disease Models, Animal
  • Dizocilpine Maleate / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Exploratory Behavior / physiology
  • Female
  • Haloperidol / pharmacology
  • Motor Activity / drug effects*
  • Neural Inhibition / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology
  • Schizophrenia / physiopathology*
  • Vitamin D Deficiency / physiopathology*

Substances

  • Antipsychotic Agents
  • Excitatory Amino Acid Antagonists
  • Dizocilpine Maleate
  • Haloperidol