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.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
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 Jun 3;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 Mar 15;242:106-11.
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 Sep 1;271:39-42.
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 Jul;220(4):2415-22.
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 May;154(5):1820-31.
Meitzen, J., Grove, D., Mermelstein, P.G. The organizational and aromatization hypotheses apply to rapid, non-classical hormone action: neonatal masculinization eliminates rapid estradiol action in female hippocampal neurons. Endocrinology 2012 Oct;153(10):4616-21.
Hedges, V.L., Ebner, T.J., Meisel, R.L., Mermelstein, P.G. The cerebellum as a target for estradiol action. Front Neuroendocrinol. 2012 Oct;33(4):403-11.
Mani, S.K., Mermelstein, P.G., Tetel, M.J., Anesetti, G. Convergence of multiple mechanisms of steroid hormone action. Hormone and Metabolic Research 44 (2012) 569-576.
Luoma, J.I., Stern, C.M., Mermelstein, P.G. Progesterone inhibition of neuronal calcium signaling underlies aspects of progesterone-mediated neuroprotection. Journal of Steroid Biochemistry and Molecular Biology 2012 Aug;131(1-2):30-6.
Srivastava, D.P., Waters, E.M., Mermelstein, P.G., Kramar, E.A., Shors, T.J., Liu, F. Rapid estrogen signaling in the brain – implications for the fine-tuning of neuronal circuitry. Journal of Neuroscience 31 (2011) 16056-16063.
Kelley, B.G., Mermelstein, P.G. Progesterone blocks multiple routes of ion flux. Molecular and Cellular Neuroscience 48 (2011) 137-141. Impact factor of the journal: 3.861
Stern, C.M., Meitzen, J., Mermelstein, P.G. Corticotropin-releasing factor and urocortin I activate CREB through functionally selective Gβγ signaling in hippocampal neurons. European Journal of Neuroscience 34 (2011) 671-681.
Luoma, J.I., Kelley, B.G., Mermelstein, P.G. Progesterone inhibition of voltage-gated calcium channels is a potential neuroprotective mechanism against excitotoxicity. Steroids 76 (2011) 845-855.
Meitzen, J., Mermelstein, P.G. Estrogen receptors stimulate brain region specific metabotropic glutamate receptors to rapidly initiate signal transduction pathways. Journal of Chemical Neuroanatomy 42 (2011) 236-241.
Fauser, B.C.J.M., Laven, J.S.E., Tarlatzis, B.C., Moley, K.H., Taylor, R.N., Berga, S.L., Mermelstein, P.G., Devroey, P., Gianaroli, L., D’Hooghe, T., Vercellini, P., Hummelshoj, L., Rubin, S., Goverde, A., De Leo, V., Petraglia, F., Sex steroid hormones and reproductive disorders: impact on women’s health. Reproductive Sciences 18 (2011) 702-713.
Stern, C.M., Luoma, J.I., Meitzen, J., Mermelstein, P.G. Corticotrophin releasing factor-induced CREB activation in striatal neurons occurs via a novel Gβγ signaling pathway. PLoS ONE 6 (2011) e18114.
Meitzen, J., Luoma, J.I., Stern, C.M., Mermelstein, P.G. 1-Adrenergic receptors activate two distinct signaling pathways in striatal neurons. Journal of Neurochemistry 116 (2011) 984-995.
Meitzen, J., Pflepsen, K.R., Stern, C.M., Meisel, R.L., Mermelstein, P.G. 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. Neuroscience Letters 487 (2011) 177-181.
Stern, C.M., Mermelstein, P.G. Caveolin regulation of neuronal intracellular signaling. Cellular and Molecular Life Sciences 67 (2010) 3785-3795.
Grove-Strawser, D., Boulware, M.I., and Mermelstein, P.G. Membrane estrogen receptors activate the metabotropic glutamate receptors mGluR5 and
mGluR3 to Bidirectionally regulate CREB phosphorylation in female rat striatal neurons. Neuroscience 170 (2010) 1045-1055.
Current Graduate Students:
Kellie Gross (Neuroscience, University of Minnesota).
Katherine Tonn (Neuroscience, University of Minnesota).
Former Graduate Students:
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).