Paul G. Mermelstein, Ph.D.

Professor and Associate Chairperson, Department of Neuroscience.

E-MAIL: [email protected]

Advising Statement: Here

Research 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.

Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

  • Chapp AD, Mermelstein PG, Thomas MJ. The ethanol metabolite acetic acid activates mouse nucleus accumbens shell medium spiny neurons. J Neurophysiol. 2021;125(2):620-627.
  • Lopresti NM, Esguerra M, Mermelstein PG. Sex differences in animal models of opioid reward. Curr Sex Health Rep. 2020;12(3):186-194.
  • 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.
  • Gross KS, Mermelstein PG. Estrogen receptor signaling through metabotropic glutamate receptors. Vitam Horm. 2020;114:211-232.
  • 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.
  • Meitzen J, Britson KA, Tuomela K, Mermelstein PG. The expression of select genes necessary for membrane-associated estrogen receptor signaling differ by sex in adult rat hippocampus. Steroids. 2019;142:21-27.
  • Gross KS, Moore KM, Meisel RL, Mermelstein PG. mGluR5 mediates dihydrotestosterone-induced nucleus accumbens structural plasticity, but not conditioned reward. Front Neurosci. 2018 Nov 20;12:855.
  • Meitzen J, Meisel RL, Mermelstein PG. Sex differences and the effects of estradiol on striatal function. Curr Opin Behav Sci. 2018;23:42-48.
  • Eisinger KRT, Woolfrey KM, Swanson SP, Schnell SA, Meitzen J, Dell'Acqua M, Mermelstein PG. Palmitoylation of caveolin-1 is regulated by the same DHHC acyltransferases that modify steroid hormone receptors. J Biol Chem. 2018;293:15901-15911.
  • Tonn Eisinger KR, Gross KS, Head BP, Mermelstein PG. Interactions between estrogen receptors and metabotropic glutamate receptors and their impact on drug addiction in females. Horm Behav. 2018;104:130-137.
  • Hedges VL, Chen G, Yu L, Krentzel AA, Starrett JR, Zhu JN, Suntharalingam P, Remage-Healey L, Wang JJ, Ebner TJ, Mermelstein PG. Local estrogen synthesis regulates parallel fiber-Purkinje cell neurotransmission within the cerebellar cortex. Endocrinology. 2018;159:1328-1338.
  • Tonn Eisinger KR, Larson EB, Boulware MI, Thomas MJ, Mermelstein PG. Membrane estrogen receptor signaling impacts the reward circuitry of the female brain to influence motivated behaviors. Steroids. 2018:133:53-59.
  • Micevych PE, Mermelstein PG, Sinchak K. Estradiol membrane-initiated signaling in the brain mediates reproduction. Trends Neurosci. 2017;40:654-666.
  • Peterson BM, Martinez LA, Meisel RL, Mermelstein PG. Estradiol impacts the endocannabinoid system in female rats to influence behavioral and structural responses to cocaine. Neuropharmacology. 2016;110(Pt A):118-124.
  • Martinez LA, Gross KS, Himmler BT, Emmitt NL, Peterson BM, Zlebnik NE, Foster Olive M, Carroll ME, Meisel RL, Mermelstein PG. Estradiol facilitation of cocaine self-administration in female rats requires activation of mGluR5. eNeuro. 2016 Oct 25;3(5):ENEURO.0140-16.2016.
  • Gross KS, Brandner DD, Martinez LA, Olive MF, Meisel RL, Mermelstein PG. Opposite effects of mGluR1a and mGluR5 activation on nucleus accumbens medium spiny neuron dendritic spine density. PLoS One. 2016 Sep 12;11(9):e0162755.
  • Peterson BM, Martinez LA, Meisel RL, Mermelstein PG. Estradiol impacts the endocannabinoid system in female rats to influence behavioral and structural responses to cocaine. Neuropharmacology. 2016;110(Pt A):118-124.
  • Peterson BM, Mermelstein PG, Meisel RL. Impact of immersion oils and mounting media on the confocal imaging of dendritic spines. J Neurosci Methods. 2015;242:106-11.
  • Peterson BM, Mermelstein PG, Meisel RL. Estradiol mediates dendritic spine plasticity in the nucleus accumbens core through activation of mGluR5. Brain Structure and Function. 2015;220:2415-2422.
  • Martinez LA, Peterson BM, Meisel RL, Mermelstein PG. Estradiol facilitation of cocaine-induced locomotor sensitization in female rats requires activation of mGluR5. Behav Brain Res. 2014;271:39-42. 

Current Graduate Students:

Julianna Goenaga (Neuroscience, University of Minnesota).

Natalie Lopresti (Steenrod) (Neuroscience, University of Minnesota).

Dieter Brandner (Neuroscience, University of Minnesota).

Former Graduate Students:

Katherine Tonn Eisinger (Ph.D. 2018, Neuroscience, University of Minnesota).

Kellie Gross (Ph.D. 2017, Neuroscience, University of Minnesota).

Brittni Peterson (Ph.D. 2016, Neuroscience, University of Minnesota)

Jessie Luoma (Ph.D. 2010, Neuroscience, University of Minnesota).

Christopher Stern (Ph.D. 2010, Neuroscience, University of Minnesota).

Rachel Groth (Ph.D. 2006, Neuroscience, University of Minnesota).

Marissa Iden Boulware (Ph.D. 2006, Neuroscience, University of Minnesota).

Jason Weick (Ph.D. 2005, Neuroscience, University of Minnesota).