Paul Mermelstein, PhD

Associate Department Head and Professor, Department of Neuroscience

Paul Mermelstein

Contact Info

Office Phone 612-624-8977

Office Address:
4-146 Jackson Hall
Minneapolis, MN 55455

Lab Address:
4-140 JacH


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.


Research Summary/Interests

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.


Chapp AD, Mermelstein PG, Thomas MJ. The ethanol metabolite acetic acid activates mouse nucleus accumbens shell medium spiny neurons. J Neurophysiol. 2021 Feb 1;125(2):620-627. doi: 10.1152/jn.00659.2020.

Huijgens PT, Snoeren EMS, Meisel RL, Mermelstein PG. Effects of gonadectomy and dihydrotestosterone on neuronal plasticity in motivation and reward related brain regions in the male rat. J Neuroendocrinol. 2021 Jan;33(1):e12918. doi: 10.1111/jne.12918.

Borland JM, Kim E, Swanson SP, Rothwell PE, Mermelstein PG, Meisel RL. Effect of Aggressive Experience in Female Syrian Hamsters on Glutamate Receptor Expression in the Nucleus Accumbens. Front Behav Neurosci. 2020 Nov 23;14:583395. doi: 10.3389/fnbeh.2020.583395.

Gross KS, Mermelstein PG. Estrogen receptor signaling through metabotropic glutamate receptors. Vitam Horm. 2020;114:211-232. doi: 10.1016/bs.vh.2020.06.003.

Lopresti NM, Esguerra M, Mermelstein PG. Sex Differences in Animal Models of Opioid Reward. Curr Sex Health Rep. 2020 Sep;12(3):186-194. doi: 10.1007/s11930-020-00266-4.

Eisinger KRT, Chapp AD, Swanson SP, Tam D, Lopresti NM, Larson EB, Thomas MJ, Lanier LM, Mermelstein PG. Caveolin-1 regulates medium spiny neuron structural and functional plasticity. Psychopharmacology (Berl). 2020 Sep;237(9):2673-2684. doi: 10.1007/s00213-020-05564-2.

Meitzen, J, Britson, KA, Tuomela, K & Mermelstein, PG 2019, 'The expression of select genes necessary for membrane-associated estrogen receptor signaling differ by sex in adult rat hippocampus', Steroids, pp. 21-27.

Gross, KS, Moore, KM, Meisel, RL & Mermelstein, PG 2018, 'mGluR5 mediates dihydrotestosterone-induced nucleus accumbens structural plasticity, but not conditioned reward' Frontiers in Neuroscience, vol. 12, no. NOV, 855.

Meitzen, J, Meisel, RL & Mermelstein, PG 2018, 'Sex differences and the effects of estradiol on striatal function' Current Opinion in Behavioral Sciences, vol. 23, pp. 42-48.

Tonn Eisinger, KR, Larson, EB, Boulware, MI, Thomas, MJ & Mermelstein, PG 2018, 'Membrane estrogen receptor signaling impacts the reward circuitry of the female brain to influence motivated behaviors' Steroids, vol. 133, pp. 53-59.

Hedges, VL, Chen, G, Yu, L, Krentzel, AA, Starrett, JR, Zhu, JN, Suntharalingam, P, Remage-Healey, L, Wang, JJ, Ebner, TJ & Mermelstein, PG 2018, 'Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission Within the Cerebellar Cortex' Endocrinology, vol. 159, no. 3, pp. 1328-1338.

Tonn Eisinger, KR, Woolfrey, KM, Swanson, SP, Schnell, SA, Meitzen, J, Dell’Acqua, M & Mermelstein, PG 2018, 'Palmitoylation of caveolin-1 is regulated by the same DHHC acyltransferases that modify steroid hormone receptors' Journal of Biological Chemistry, vol. 293, no. 41, pp. 15901-15911.

Tonn Eisinger, KR, Gross, KS, Head, BP & Mermelstein, PG 2018, 'Interactions between estrogen receptors and metabotropic glutamate receptors and their impact on drug addiction in females' Hormones and Behavior, vol. 104, pp. 130-137.

Micevych, PE, Mermelstein, PG & Sinchak, K 2017, 'Estradiol Membrane-Initiated Signaling in the Brain Mediates Reproduction' Trends in Neurosciences, vol. 40, no. 11, pp. 654-666.

Meitzen, J, Britson, KA, Tuomela, K & Mermelstein, PG 2019, 'The expression of select genes necessary for membrane-associated estrogen receptor signaling differ by sex in adult rat hippocampus' Steroids, vol. 142, pp. 21-27.

Peterson, BM, Martinez, LA, Meisel, RL & Mermelstein, PG 2016, 'Estradiol impacts the endocannabinoid system in female rats to influence behavioral and structural responses to cocaine' Neuropharmacology, vol. 110, pp. 118-124.



NSCI 1001: Fundamental Neuroscience (Fall semester)