D-serine prevents cognitive deficits induced by acute stress

Neuropharmacology. 2014 Nov:86:1-8. doi: 10.1016/j.neuropharm.2014.06.021. Epub 2014 Jun 28.

Abstract

Increasing evidence indicates that acute stress disrupts cognitive functions mediated by glutamate-NMDA receptors, although the mechanisms are not fully understood. Here we investigated whether d-serine and glycine, the endogenous co-agonists of the NMDA receptor, are regulated by acute stress. We studied the biochemical and behavioral effects of acute restraint stress in C57BL/6 mice. Acute restraint stress decreased d-serine levels in the prefrontal cortex and glycine levels in the hippocampus. Behaviorally, acute stress impaired memory consolidation in the object recognition task and prepulse inhibition of the startle response. Importantly, d-serine administration (1 g/kg, i.p.) prevented both stress-induced impairments. Taken together, our results show for the first time an interplay between stress and d-serine and warrant further research on the role of d-serine in stress-related disorders.

Keywords: Cognition; NMDA receptor; Object recognition task; Prepulse inhibition; Serine racemase; Stress; d-serine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Cognition Disorders / drug therapy
  • Cognition Disorders / etiology
  • Cognition Disorders / physiopathology*
  • Corticosterone / blood
  • Disease Models, Animal
  • Glycine / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / physiopathology*
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Mice, Inbred C57BL
  • Nootropic Agents / administration & dosage
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology*
  • Prepulse Inhibition / drug effects
  • Prepulse Inhibition / physiology
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology
  • Restraint, Physical
  • Serine / administration & dosage
  • Serine / metabolism*
  • Stress, Psychological / complications
  • Stress, Psychological / physiopathology*
  • Stress, Psychological / psychology

Substances

  • Nootropic Agents
  • Serine
  • Glycine
  • Corticosterone