Paul Mermelstein is a professor in the Department of Neuroscience. His laboratory researches sex differences in the brain. Specifically, how sex hormones (estrogen in females, testosterone in males) alter the synaptic connections in the brain to influence motivated behaviors. He and his team have discovered that when estrogen concentrations rise in females, their vulnerability to abuse addictive drugs increases. They are seeking to determine the mechanisms by which estrogens impart vulnerability to drug addiction, and ways to circumvent these changes in brain plasticity, ultimately in hopes of improving therapeutic interventions.
Estrogen Potentiation of Female Drug Addiction Research in my laboratory focuses on the effects of steroid hormones (particularly estrogens) on motivated behaviors. Of particular interest has been our study of membrane estrogen receptor signaling across the nervous system. We were the first to describe that estrogen receptor alpha and beta can functionally interact with metabotropic glutamate receptors (mGluRs), leading to glutamate-independent mGluR signaling. Throughout the female nervous system, estrogen receptors (ER) couple to both group I (mGluR1a, mGluR5) and group II (mGluR2, mGluR3) mGluRs, leading to changes in second messenger signaling, cell excitability, neurotransmission and ultimately behavior. Current projects in the lab center on understanding the mechanism by which ERs are trafficked to the surface membrane of neurons, allowing functional coupling with mGluRs. Recent findings suggest that palmitoylation of both ERs and structural caveolin proteins are essential for ER activation of mGluR signaling. Additionally, ER/mGluR signaling in the female nucleus accumbens appears responsible for women exhibiting heightened vulnerability to drug abuse. Through inhibition of ER/mGluR signaling, we are able to eliminate estrogen-mediated potentiated responsiveness to psychostimulants in models of drug addiction.