Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome

Neuron. 2005 Mar 3;45(5):753-64. doi: 10.1016/j.neuron.2005.01.038.

Abstract

Fragile X syndrome is a leading heritable cause of mental retardation that results from the loss of FMR1 gene function. A Drosophila model for Fragile X syndrome, based on the loss of dfmr1 activity, exhibits phenotypes that bear similarity to Fragile X-related symptoms. Herein, we demonstrate that treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium can rescue courtship and mushroom body defects observed in these flies. Furthermore, we demonstrate that dfmr1 mutants display cognitive deficits in experience-dependent modification of courtship behavior, and treatment with mGluR antagonists or lithium restores these memory defects. These findings implicate enhanced mGluR signaling as the underlying cause of the cognitive, as well as some of the behavioral and neuronal, phenotypes observed in the Drosophila Fragile X model. They also raise the possibility that compounds having similar effects on metabotropic glutamate receptors may ameliorate cognitive and behavioral defects observed in Fragile X patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Courtship* / psychology
  • Disease Models, Animal*
  • Drosophila
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Female
  • Fragile X Syndrome / drug therapy*
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / psychology
  • Lithium / pharmacology
  • Lithium / therapeutic use
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Mushroom Bodies / drug effects
  • Mushroom Bodies / physiology*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Synapses / drug effects
  • Synapses / physiology

Substances

  • Excitatory Amino Acid Antagonists
  • Lithium