Interactions between estrogen receptors and metabotropic glutamate receptors and their impact on drug addiction in females

Horm Behav. 2018 Aug;104:130-137. doi: 10.1016/j.yhbeh.2018.03.001. Epub 2018 Mar 10.


Contribution to Special Issue on Fast effects of steroids. Estrogen receptors α and β (ERα and ERβ) have a unique relationship with metabotropic glutamate receptors (mGluRs) in the female rodent brain such that estradiol is able to recruit intracellular G-protein signaling cascades to influence neuronal physiology, structure, and ultimately behavior. While this association between ERs and mGluRs exists in many cell types and brain regions, its effects are perhaps most striking in the nucleus accumbens (NAc). This review will discuss the original characterization of ER/mGluR signaling and how estradiol activity in the NAc confers increased sensitivity to drugs of abuse in females through this mechanism.

Keywords: Brain; Drug addiction; Estrogen receptors; mGluR.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Estradiol / pharmacology
  • Female
  • Neurons / drug effects
  • Neurons / metabolism
  • Receptors, Estrogen / metabolism*
  • Receptors, Metabotropic Glutamate / metabolism*
  • Rodentia
  • Sex Characteristics
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Substance-Related Disorders / etiology
  • Substance-Related Disorders / metabolism*


  • Receptors, Estrogen
  • Receptors, Metabotropic Glutamate
  • Estradiol