Paul G. Mermelstein, Ph.D.

Professor and Associate Chairperson, Department of Neuroscience.


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.)

  • 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 Mar 10. PMID 29505763
  • 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 May:133:53-59.  PMID 29195840.
  • Micevych PE, Mermelstein PG, Sinchak K. Estradiol membrane-initiated signaling in the brain mediates reproduction. Trends Neurosci. 2017;40(11):654-666.
  • 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. 2017 Sep 28. pii: S0039-128X(17)30179-4.
  • 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). pii: 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.
  • Meitzen J, Perry AN, Westenbroek C, Hedges VL, Becker JB, Mermelstein PG. Enhanced striatal β1-adrenergic receptor expression following hormone loss in adulthood is programmed by both early sexual differentiation and puberty: a study of humans and rats. Endocrinology. 2013;154:1820-1831.
  • Meitzen J, Grove D, Mermelstein PG. The organizational and aromatization hypotheses apply to rapid, non-classical hormone action: neonatal masculinization eliminates rapid estradiol action in female hippocampal neurons. Endocrinology 2012;153:4616-4621.  
  • Hedges VL, Ebner TJ, Meisel RL, Mermelstein PG. The cerebellum as a target for estradiol action. Front Neuroendocrinol. 2012;33(4):403-411.   
  • Mani SK, Mermelstein PG, Tetel MJ, Anesetti G. Convergence of multiple mechanisms of steroid hormone action. Horm Metab Res. 2012;44(8):569-76.        
  • Luoma JI, Stern CM, Mermelstein PG. Progesterone inhibition of neuronal calcium signaling underlies aspects of progesterone-mediated neuroprotection. J Steroid Biochem Mol Biol. 2012;131:30-36.
  • Srivastava DP, Waters EM, Mermelstein PG, Kramár EA, Shors TJ, Liu F. Rapid estrogen signaling in the brain – implications for the fine-tuning of neuronal circuitry. J Neurosci. 2011;31:16056-16063.
  • Kelley BG, Mermelstein PG. Progesterone blocks multiple routes of ion flux. Mol Cell Neurosci. 2011;48:137-141
  • Stern CM, Meitzen J, Mermelstein PG. Corticotropin-releasing factor and urocortin I activate CREB through functionally selective Gβγ signaling in hippocampal pyramidal neurons. Eur J Neurosci. 2011;34:671-681.
  • Luoma JI, Stern CM, Mermelstein PG. Progesterone inhibition of voltage-gated calcium channels is a potential neuroprotective mechanism against excitotoxicity. Steroids 2011;76:845-855.
  • Meitzen J, Mermelstein PG. Estrogen receptors stimulate brain region specific metabotropic glutamate receptors to rapidly initiate signal transduction pathways. J Chem Neuroanat. 2011;42:236-241.
  • Fauser BC, Laven JS, Tarlatzis BC, Moley KH, Critchley HO, Taylor RN, Berga SL, Mermelstein PG, Devroey P, Gianaroli L, D'Hooghe T, Vercellini P, Hummelshoj L, Rubin S, Goverde AJ, De Leo V, Petraglia F. Sex steroid hormones and reproductive disorders: impact on women’s health. Reprod Sci. 2011;18(8):702-12.    
  • Stern CM, Luoma JI, Meitzen J, Mermelstein PG. Corticotropin releasing factor-induced CREB activation in striatal neurons occurs via a novel Gβγ signaling pathway. PLoS ONE 2011;e18114.         
  • Meitzen J, Luoma JI, Stern CM, Mermelstein PG. β1-Adrenergic receptors activate two distinct signaling pathways in striatal neurons. J Neurochem. 2011;116:984-995.           
  • Meitzen J, Pflepsen KR, Stern CM, Meisel RL, Mermelstein PG. Measurements of neuron soma size and density in the rat dorsal striatum, nucleus accumbens core and nucleus accumbens shell: differences between striatal region and brain hemisphere, but not sex. Neurosci Lett 2011;487:177-181.

Current Graduate Students:

Natalie Steenrod (Neuroscience, University of Minnesota

Katherine Tonn (Neuroscience, University of Minnesota).

Former Graduate Students:

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).