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Ellen Unterwald

Ellen unterwald, PhD


Professor, Pharmacology

Director, Center for Substance Abuse Research

Telephone:  215-707-1681

Fax:  215-707-6661

Email: ellen.unterwald@temple.edu


Department of Pharmacology

Center for Substance Abuse Research


Educational Background:


University of Rhode Island; B.S. Pharmacy 1980


Boston University School of Medicine; Ph.D. Pharmacology 1985


Albert Einstein College of Medicine, Department of Neuroscience; Postdoctoral Fellow 1988


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Research Interests:


Brain Slices

Our research investigates cellular and molecular mechanisms involved in drug addiction. We are particularly interested in neuroadaptations in specific receptors, signal transduction pathways, and transcription factors that result from exposure to psychostimulants (eg, cocaine and amphetamine) and opiates (eg, morphine and heroin). These adaptations are important as they mediate the processes of drug tolerance, dependence, sensitization, withdrawal and craving, which form the basis of addictive disease. The role of these molecules and pathways in drug-induced behavior is also investigated using several relevant animal models. Some of these studies focus on the childhood and adolescent periods, where they have direct relevance to both the therapeutic use of psychostimulants in children, such as during the treatment of attention deficit hyperactivity disorder (ADHD), and the illicit abuse of these substances by young people. Other studies investigate the relationship between stress, anxiety, and relapse to drug use.  It is anticipated that by identifying neurobiological alterations that occur during exposure to drugs of abuse, the molecular mechanisms of drug addiction will be elucidated and effective therapeutic strategies will follow. These research projects have been supported in part by grants from the National Institute on Drug Abuse (NIDA),the Department of Health, and Temple University.


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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

26115790. Enman NM, Arthur K, Ward SJ, Perrine SA, Unterwald EM, Anhedonia, Reduced Cocaine Reward, and Dopamine Dysfunction in a Rat Model of Posttraumatic Stress Disorder. Biol Psychiatry :()2015 May 6

26077147. Barr JL, Deliu E, Brailoiu GC, Zhao P, Yan G, Abood ME, Unterwald EM, Brailoiu E, Mechanisms of activation of nucleus accumbens neurons by cocaine via sigma-1 receptor-inositol 1,4,5-trisphosphate-transient receptor potential canonical channel pathways. Cell Calcium :()2015 May 27

25656481. Craige CP, Lewandowski S, Kirby LG, Unterwald EM, Dorsal raphe 5-HT(2C) receptor and GABA networks regulate anxiety produced by cocaine withdrawal. Neuropharmacology 93:(41-51)2015 Jun

25294309. Barr JL, Unterwald EM, Activity-regulated gene expression in immature neurons in the dentate gyrus following re-exposure to a cocaine-paired environment. Hippocampus 25:3(354-62)2015 Mar

24911954. Parikh V, Naughton SX, Shi X, Kelley LK, Yegla B, Tallarida CS, Rawls SM, Unterwald EM, Cocaine-induced neuroadaptations in the dorsal striatum: glutamate dynamics and behavioral sensitization. Neurochem Int 75:(54-65)2014 Sep

24832868. Barr JL, Forster GL, Unterwald EM, Repeated cocaine enhances ventral hippocampal-stimulated dopamine efflux in the nucleus accumbens and alters ventral hippocampal NMDA receptor subunit expression. J Neurochem 130:4(583-90)2014 Aug

24595501. Shi X, Miller JS, Harper LJ, Poole RL, Gould TJ, Unterwald EM, Reactivation of cocaine reward memory engages the Akt/GSK3/mTOR signaling pathway and can be disrupted by GSK3 inhibition. Psychopharmacology (Berl) 231:16(3109-18)2014 Aug

24505362. Miller JS, Barr JL, Harper LJ, Poole RL, Gould TJ, Unterwald EM, The GSK3 signaling pathway is activated by cocaine and is critical for cocaine conditioned reward in mice. PLoS One 9:2(e88026)2014

24333548. Enman NM, Zhang Y, Unterwald EM, Connecting the pathology of posttraumatic stress and substance use disorders: monoamines and neuropeptides. Pharmacol Biochem Behav 117:(61-9)2014 Feb

23103406. Craige CP, Unterwald EM, Serotonin (2C) receptor regulation of cocaine-induced conditioned place preference and locomotor sensitization. Behav Brain Res 238:(206-10)2013 Feb 1

22649795. Enman NM, Unterwald EM, Inhibition of GSK3 attenuates amphetamine-induced hyperactivity and sensitization in the mouse. Behav Brain Res 231:1(217-25)2012 May 16

21524862. Rasmussen B, Unterwald EM, Rawls SM, Glutamate transporter subtype 1 (GLT-1) activator ceftriaxone attenuates amphetamine-induced hyperactivity and behavioral sensitization in rats. Drug Alcohol Depend 118:2-3(484-8)2011 Nov 1

20807318. Nwaneshiudu CA, Unterwald EM, NK-3 receptor antagonism prevents behavioral sensitization to cocaine: a role of glycogen synthase kinase-3 in the nucleus accumbens. J Neurochem 115:3(635-42)2010 Nov

20730419. Randall-Thompson JF, Pescatore KA, Unterwald EM, A role for delta opioid receptors in the central nucleus of the amygdala in anxiety-like behaviors. Psychopharmacology (Berl) 212:4(585-95)2010 Dec

20383795. Rasmussen BA, Baron DA, Kim JK, Unterwald EM, Rawls SM, -Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats. Amino Acids 40:2(761-4)2011 Feb

20347018. Miller JS, Tallarida RJ, Unterwald EM, Inhibition of GSK3 attenuates dopamine D1 receptor agonist-induced hyperactivity in mice. Brain Res Bull 82:3-4(184-7)2010 May 31

20026091. Trecki J, Brailoiu GC, Unterwald EM, Localization of CXCR4 in the forebrain of the adult rat. Brain Res 1315:(53-62)2010 Feb 22

19879869. Rasmussen BA, Unterwald EM, Kim JK, Rawls SM, Methanandamide blocks amphetamine-induced behavioral sensitization in rats. Eur J Pharmacol 627:1-3(150-5)2010 Feb 10

19733208. Huang P, Liu-Chen LY, Unterwald EM, Cowan A, Hyperlocomotion and paw tremors are two highly quantifiable signs of SR141716-precipitated withdrawal from delta9-tetrahydrocannabinol in C57BL/6 mice. Neurosci Lett 465:1(66-70)2009 Nov 6

19699185. Soderman AR, Unterwald EM, Cocaine-induced mu opioid receptor occupancy within the striatum is mediated by dopamine D2 receptors. Brain Res 1296:(63-71)2009 Nov 3

19562697. Schroeder JA, McCafferty MR, Unterwald EM, Regulation of dynamin 2 and G protein-coupled receptor kinase 2 in rat nucleus accumbens during acute and repeated cocaine administration. Synapse 63:10(863-70)2009 Oct

19500601. Nwaneshiudu CA, Unterwald EM, Blockade of neurokinin-3 receptors modulates dopamine-mediated behavioral hyperactivity. Neuropharmacology 57:3(295-301)2009 Sep

19401177. Rasmussen BA, Kim E, Unterwald EM, Rawls SM, Methanandamide attenuates cocaine-induced hyperthermia in rats by a cannabinoid CB1-dopamine D2 receptor mechanism. Brain Res 1260:(7-14)2009 Mar 13

19328817. Miller JS, Tallarida RJ, Unterwald EM, Cocaine-induced hyperactivity and sensitization are dependent on GSK3. Neuropharmacology 56:8(1116-23)2009 Jun

19303923. Trecki J, Unterwald EM, Modulation of cocaine-induced activity by intracerebral administration of CXCL12. Neuroscience 161:1(13-22)2009 Jun 16

21768981. Unterwald EM, Naltrexone in the treatment of alcohol dependence. J Addict Med 2:3(121-7)2008 Sep

18717814. Perrine SA, Miller JS, Unterwald EM, Cocaine regulates protein kinase B and glycogen synthase kinase-3 activity in selective regions of rat brain. J Neurochem 107:2(570-7)2008 Oct

18550291. Soderman AR, Unterwald EM, Cocaine reward and hyperactivity in the rat: sites of mu opioid receptor modulation. Neuroscience 154:4(1506-16)2008 Jul 17

18234897. Niculescu M, Perrine SA, Miller JS, Ehrlich ME, Unterwald EM, Trk: a neuromodulator of age-specific behavioral and neurochemical responses to cocaine in mice. J Neurosci 28:5(1198-207)2008 Jan 30

18045627. Perrine SA, Sheikh IS, Nwaneshiudu CA, Schroeder JA, Unterwald EM, Withdrawal from chronic administration of cocaine decreases delta opioid receptor signaling and increases anxiety- and depression-like behaviors in the rat. Neuropharmacology 54:2(355-64)2008 Feb

17980352. Huang P, Xu W, Yoon SI, Chen C, Chong PL, Unterwald EM, Liu-Chen LY, Agonist treatment did not affect association of mu opioid receptors with lipid rafts and cholesterol reduction had opposite effects on the receptor-mediated signaling in rat brain and CHO cells. Brain Res 1184:(46-56)2007 Dec 12

17980152. Huang P, Chen C, Xu W, Yoon SI, Unterwald EM, Pintar JE, Wang Y, Chong PL, Liu-Chen LY, Brain region-specific N-glycosylation and lipid rafts association of the rat mu opioid receptor. Biochem Biophys Res Commun 365:1(82-8)2008 Jan 4

17687547. Schroeder JA, Hummel M, Simpson AD, Sheikh R, Soderman AR, Unterwald EM, A role for mu opioid receptors in cocaine-induced activity, sensitization, and reward in the rat. Psychopharmacology (Berl) 195:2(265-72)2007 Dec

16893609. Hummel M, Schroeder J, Liu-Chen LY, Cowan A, Unterwald EM, An antisense oligodeoxynucleotide to the mu opioid receptor attenuates cocaine-induced behavioral sensitization and reward in mice. Neuroscience 142:2(481-91)2006 Oct 13

16650615. Wang Y, Dun SL, Huang P, Chen C, Chen Y, Unterwald EM, Dun NJ, Van Bockstaele EJ, Liu-Chen LY, Distribution and ultrastructural localization of GEC1 in the rat CNS. Neuroscience 140:4(1265-76)2006 Jul 21

16491101. Perrine SA, Hoshaw BA, Unterwald EM, Delta opioid receptor ligands modulate anxiety-like behaviors in the rat. Br J Pharmacol 147:8(864-72)2006 Apr

16199081. Niculescu M, Ehrlich ME, Unterwald EM, Age-specific behavioral responses to psychostimulants in mice. Pharmacol Biochem Behav 82:2(280-8)2005 Oct

15772255. Muller DL, Unterwald EM, D1 dopamine receptors modulate deltaFosB induction in rat striatum after intermittent morphine administration. J Pharmacol Exp Ther 314:1(148-54)2005 Jul

15710239. Perrine SA, Schroeder JA, Unterwald EM, Behavioral sensitization to binge-pattern cocaine administration is not associated with changes in protein levels of four major G-proteins. Brain Res Mol Brain Res 133:2(224-32)2005 Feb 18

15388288. Schroeder JA, Hummel M, Unterwald EM, Disruption of G(i/o) protein signaling in the nucleus accumbens results in a D1 dopamine receptor-mediated hyperactivity. Pharmacol Biochem Behav 79:1(93-9)2004 Sep

15219727. Schroeder JA, Hummel M, Unterwald EM, Repeated intracerebroventricular forskolin administration enhances behavioral sensitization to cocaine. Behav Brain Res 153:1(255-60)2004 Aug 12

15056728. Muller DL, Unterwald EM, In vivo regulation of extracellular signal-regulated protein kinase (ERK) and protein kinase B (Akt) phosphorylation by acute and chronic morphine. J Pharmacol Exp Ther 310:2(774-82)2004 Aug

15051160. Hummel M, Ansonoff MA, Pintar JE, Unterwald EM, Genetic and pharmacological manipulation of mu opioid receptors in mice reveals a differential effect on behavioral sensitization to cocaine. Neuroscience 125:1(211-20)2004

14741752. Unterwald EM, Ivkovic S, Cuntapay M, Stroppolo A, Guinea B, Ehrlich ME, Prenatal exposure to cocaine decreases adenylyl cyclase activity in embryonic mouse striatum. Brain Res Dev Brain Res 147:1-2(67-75)2003 Dec 30

12591125. Hummel M, Unterwald EM, Intra-accumbens pertussis toxin sensitizes rats to the locomotor activating effects of a single cocaine challenge. Brain Res 965:1-2(100-7)2003 Mar 7

12422370. Schroeder JA, Niculescu M, Unterwald EM, Cocaine alters mu but not delta or kappa opioid receptor-stimulated in situ [35S]GTPgammaS binding in rat brain. Synapse 47:1(26-32)2003 Jan

11920678. Hummel M, Unterwald EM, D1 dopamine receptor: a putative neurochemical and behavioral link to cocaine action. J Cell Physiol 191:1(17-27)2002 Apr

11458541. Unterwald EM, Regulation of opioid receptors by cocaine. Ann N Y Acad Sci 937:(74-92)2001 Jun

11325352. Unterwald EM, Kreek MJ, Cuntapay M, The frequency of cocaine administration impacts cocaine-induced receptor alterations. Brain Res 900:1(103-9)2001 May 4

10698003. Unterwald EM, Cuntapay M, Dopamine-opioid interactions in the rat striatum: a modulatory role for dopamine D1 receptors in delta opioid receptor-mediated signal transduction. Neuropharmacology 39:3(372-81)2000 Jan 28

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Laboratory PersonneL:



Xiangdang Shi, PhD – Assistant Scientist
Jeffrey Barr, PhD – Postdoctoral Fellow
Menahem Doura, PhD – Postdoctoral Fellow
Nicole Enman – PhD Student
Caryne Craige –PhD Student

Mary McCafferty – Research Technician

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