Estradiol mediates dendritic spine plasticity in the nucleus accumbens core through activation of mGluR5

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Accumulating evidence from human and rodent studies suggests that females are more sensitive to the motivating and rewarding properties of drugs of abuse. Numerous reports implicate estradiol in enhancing drug-related responses in females, yet the neurobiological mechanisms underlying this effect of estradiol are unknown. Because dendritic spine plasticity in the nucleus accumbens (NAc) is linked to the addictive effects of drugs, we examined the influence of estradiol on dendritic spines in this region. Previously our laboratory demonstrated that in female medium spiny neurons, estradiol activates metabotropic glutamate receptor subtype five (mGluR5), a G protein-coupled receptor already implicated in the etiology of drug addiction. Thus, we sought to determine whether mGluR5 is a part of the mechanism by which estradiol affects dendritic spine density in the NAc. To test this hypothesis, ovariectomized female rats were treated with the mGluR5 antagonist, MPEP, or vehicle prior to estradiol (or oil) treatment and 24 h later dendritic spine density was evaluated by DiI labeling and confocal microscopy. We found that estradiol decreased dendritic spine density in the NAc core and that pretreatment with MPEP blocked this effect. In contrast, MPEP had no effect on dendritic spine density in the NAc shell or CA1 region of the hippocampus, two regions in which estradiol increased the density of dendritic spines. As dendritic spine plasticity in the NAc core has behavioral consequences for drug addiction, these data provide a clue as to how estradiol acts in females to enhance behavioral responses to drugs of abuse.

Original languageEnglish (US)
Pages (from-to)2415-2422
Number of pages8
JournalBrain Structure and Function
Issue number4
StatePublished - Jul 27 2015

Bibliographical note

Funding Information:
This material is based upon work supported by the National Institutes of Health DA035008 and National Science Foundation IOS-114616 and Grant No. 00006595. We would like to thank Dr. Luis Martinez for advice and technical assistance.

Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.


  • Drug addiction
  • Estrogen
  • Medium spiny neuron
  • mGluR


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