Sex differences in the manifestation, prevalence, and progression of dopamine‐related diseases have been documented, suggesting a role of gonadal hormones (Bodzean et al., 2014; Kokras and Dalla, 2014). Although dopamine neurons are sensitive to estradiol (E2), main estrogen metabolite in women, it is uncertain how estradiol affects the function and survival of dopamine neurons. Eight metabotropic glutamate receptor subtypes (mGluR1‐8) have been identified and classified in three different groups according to the receptor signal transduction, pharmacology and amino acid sequence homology. mGluR subtypes are important modulators of cell proliferation (Plenz and Kitaj 1998), neuronal excitability and neurotransmitter release (Meltzer et al. 1997; Mercuri et al. 1993). The objective of our research was to study the effects of E2 on the expression of group I (mGluR1 and 5) and group II (mGluR2 and 3) mGluRs. We hypothesized that E2 increases the protein expression of group I mGluRs without affecting the expression of group II mGluRs. To test our hypothesis cultures of embryonic mesencephalic dopamine neurons were treated with either cyclodextrin or E2 at different concentrations (10nM and 10μM). Immunocytochemistry experiments showed the expression of estrogen receptors alpha (ERα), mGluR1, and mGluR2/3 subtypes in our experimental cellular model. Western bot analyses demonstrated that E2 treatment upregulates the expression of mGluR1, a group I mGluR subtype, but not group II mGluRs subtypes. Estradiol's effect was concentration dependent producing mGluR1 upregulation at 10μM but not at 10nM (F(2,9)=4.03, p=0.05). Changes in mGluRs protein expression by differences in estradiol levels may underlay variations in cells excitability and function, inducing sex differences in the neurophysiology of dopamine neurons.Support or Funding InformationThis research was supported by the Deanship of Academic Affairs of the University of Puerto Rico, Cayey Campus (FIDI‐UPR CAYEY 2017–2018) and in part by Puerto Rico Center for Environmental Neuroscience (NSF grant HRD 1137725). We also thank Barreto‐Estrada J and Perez‐Acevedo N for her support, collaboration and mentoring during this project.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.