caa a22 4500 606202749 CHVBK 20210128100954.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00429-014-0794-9 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0794-9 Estradiol mediates dendritic spine plasticity in the nucleus accumbens core through activation of mGluR5 [Elektronische Daten] [Brittni Peterson, Paul Mermelstein, Robert Meisel] 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 24h 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. Springer-Verlag Berlin Heidelberg, 2014 Estrogen nationallicence Drug addiction nationallicence Medium spiny neuron nationallicence mGluR nationallicence Peterson Brittni Department of Neuroscience and Graduate Program in Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church Street SE, 55455, Minneapolis, MN, USA aut Mermelstein Paul Department of Neuroscience and Graduate Program in Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church Street SE, 55455, Minneapolis, MN, USA aut Meisel Robert Department of Neuroscience and Graduate Program in Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church Street SE, 55455, Minneapolis, MN, USA aut Brain Structure and Function Springer Berlin Heidelberg 220/4(2015-07-01), 2415-2422 1863-2653 220:4<2415 2015 220 429 https://doi.org/10.1007/s00429-014-0794-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0794-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Peterson Brittni Department of Neuroscience and Graduate Program in Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church Street SE, 55455, Minneapolis, MN, USA aut NATIONALLICENCE 700 1- Mermelstein Paul Department of Neuroscience and Graduate Program in Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church Street SE, 55455, Minneapolis, MN, USA aut NATIONALLICENCE 700 1- Meisel Robert Department of Neuroscience and Graduate Program in Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church Street SE, 55455, Minneapolis, MN, USA aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/4(2015-07-01), 2415-2422 1863-2653 220:4<2415 2015 220 429