Zinc supplementation in rats impairs hippocampal-dependent memory consolidation and dampens post-traumatic recollection of stressful event

Eur Neuropsychopharmacol. 2016 Jun;26(6):1070-82. doi: 10.1016/j.euroneuro.2015.12.041. Epub 2016 Jan 7.

Abstract

Zinc is a trace element important for synaptic plasticity, learning and memory. Zinc deficiency, both during pregnancy and after birth, impairs cognitive performance and, in addition to memory deficits, also results in alterations of attention, activity, neuropsychological behavior and motor development. The effects of zinc supplementation on cognition, particularly in the adult, are less clear. We demonstrate here in adult rats, that 4 week-long zinc supplementation given by drinking water, and approximately doubling normal daily intake, strongly impairs consolidation of hippocampal-dependent memory, tested through contextual fear conditioning and inhibitory avoidance. Furthermore, the same treatment started after memory consolidation of training for the same behavioral tests, substantially dampens the recall of the stressful event occurred 4 weeks before. A molecular correlate of the amnesic effect of zinc supplementation is represented by a dysregulated function of GSK-3ß in the hippocampus, a kinase that participates in memory processes. The possible relevance of these data for humans, in particular regarding post-traumatic stress disorders, is discussed in view of future investigation.

Keywords: Contextual fear conditioning; GSK-3ß; Inhibitory avoidance; Long-term treatment; Phosphorylation; Zinc.

MeSH terms

  • Animals
  • Conditioning, Psychological / drug effects
  • Dietary Supplements*
  • Fear / drug effects
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • MAP Kinase Signaling System / drug effects
  • Male
  • Memory Consolidation / drug effects*
  • Neurogenesis / drug effects
  • Rats
  • Rats, Wistar
  • Stress Disorders, Post-Traumatic / psychology
  • Stress, Psychological / psychology*
  • Trace Elements / blood
  • Trace Elements / pharmacology*
  • Wounds and Injuries / psychology*
  • Zinc / blood
  • Zinc / pharmacology*

Substances

  • Trace Elements
  • Glycogen Synthase Kinase 3
  • Zinc