ELENA H. CHARTOFF, PHD
- Harvard title(s): Assistant Professor of Psychiatry
- Email: echartoff@mclean.harvard.edu
- Telephone: (617) 855-2022
- Fax: (617) 855-2023
- Office Address: Behavioral Genetics Laboratory (MRC 218)
- Bio:
Elena received her B.S. in Biology from Carnegie Mellon University and her Ph.D. in Neurobiology and Behavior from the University of Washington. Her graduate thesis examined the regulation and role of the neuropeptide neurotensin in the striatum of rodent models of psychosis. Elena then trained as a postdoctoral fellow in Bill Carlezon's laboratory at McLean Hospital where she began her work studying the neurobiological mechanisms underlying addiction and depression. As a postdoc, Elena was awarded an NRSA postdoctoral fellowship from the National Institute on Drug Abuse (NIDA) as well as the Kaneb Fellowship in Psychiatry, which specifically supports research on depression at McLean Hospital.
Research:
Our research focuses on molecular and behavioral correlates of depressive-like states that accompany withdrawal from drugs of abuse in rodents. Alleviation of aversive withdrawal symptoms is thought to be a primary motivation for continued drug taking and relapse (see Figure 1). The mesolimbic dopamine system, which includes the nucleus accumbens, plays an important role in both the rewarding and aversive effects of drugs such as morphine and cocaine. We work closely with the Behavioral Genetics Laboratory, directed by Dr. Bill Carlezon and the Molecular Pharmacology Laboratory, directed by Dr. Bruce Cohen, to conduct two primary lines of research. First, we are investigating the role of nucleus accumbens AMPA glutamate receptors in mediating morphine withdrawal-associated aversive states. We focus on the negative affective signs of withdrawal through the use of behavioral assays sensitive to rewarding and aversive states (place conditioning and rewarding brain stimulation). Second, we are studying how kappa opioid receptor systems and ERK modulate cocaine reward and cocaine withdrawal-induced depressive-like states. To accomplish this, we are measuring the effects of kappa opioid receptor ligands on acute cocaine reward and on withdrawal from binge cocaine treatments using intracranial rewarding brain stimulation. We are also using viral vectors to manipulate ERK function in the nucleus accumbens and measuring the effects on reward function. Together, these studies may lead to an increased understanding of the mechanisms underlying addiction. This work may lead to new pharmacotherapies that can alleviate aversive and dysphoric states associated with drug withdrawal and perhaps reduce relapse to drug taking.
Figure 1
Figure 2
Personnel:
David Potter, M.S.; Research Lab Manager
The Behavioral Genetics Laboratory
Elena Chartoff Group
(click to enlarge)
Shayla Russell; Research Assistant
Angela M. Sparrow, Ph.D., Postdoctoral Fellow
Research Support:
National Institute on Drug Abuse (NIDA)
National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD)
Morris-Braun Foundation
- Publications: Pubmed search for "Chartoff E"
Selected references:- Adams MR, Brandon EP, Chartoff EH, Idzerda RL, Dorsa DM, McKnight GS. Loss of haloperidol induced gene expression and catalepsy in protein kinase A-deficient mice. Proc Natl Acad Sci U S A. 1997;94(22):12157-61.
- Chartoff EH, Ward RP, Dorsa DM. Role of adenosine and N-methyl-D-aspartate receptors in mediating haloperidol-induced gene expression and catalepsy. J Pharmacol Exp Ther. 1999;291(2):531-7.
- Chartoff EH, Marck BT, Matsumoto AM, Dorsa DM, Palmiter RD. Induction of stereotypy in dopamine-deficient mice requires striatal D1 receptor activation. Proc Natl Acad Sci U S A. 2001;98(18):10451-6.
- Chartoff EH, Papadopoulou M, Konradi C, Carlezon WA. Dopamine-dependent increases in phosphorylation of cAMP response element binding protein (CREB) during precipitated morphine withdrawal in primary cultures of rat striatum. J Neurochem. 2003;87(1):107-18. PMID: 12969258
- Chartoff EH, Heusner CL, Palmiter RD. Dopamine is not required for the hyperlocomotor response to NMDA receptor antagonists. Neuropsychopharmacology. 2005;30(7):1324-33. PMID: 15688082
- Goussakov I, Chartoff EH, Tsvetkov E, Gerety LP, Meloni EG, Carlezon WA, Bolshakov VY. LTP in the lateral amygdala during cocaine withdrawal. Eur J Neurosci. 2006;23(1):239-50.
- Chartoff EH, Mague SD, Barhight MF, Smith AM, Carlezon WA. Behavioral and molecular effects of dopamine D1 receptor stimulation during naloxone-precipitated morphine withdrawal. J Neurosci. 2006;26(24):6450-7.
- Chartoff EH, Pliakas AM, Carlezon WA. Microinjection of the L-type calcium channel antagonist diltiazem into the ventral nucleus accumbens shell facilitates cocaine-induced conditioned place preferences. Biol Psychiatry. 2006;59(12):1236-9.
- Carlezon WA, Chartoff EH. Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation. Nat Protoc. 2007;2(11):2987-95.
- Chartoff EH, Potter D, Damez-Werno D, Cohen BM, Carlezon WA. Exposure to the selective kappa-opioid receptor agonist salvinorin A modulates the behavioral and molecular effects of cocaine in rats. Neuropsychopharmacology. 2008;33(11):2676-87.
- Chartoff EH, Barhight MF, Mague SD, Sawyer AM, Carlezon WA. Anatomically dissociable effects of dopamine D1 receptor agonists on reward and relief of withdrawal in morphine-dependent rats. Psychopharmacology (Berl). 2009;204(2):227-239.
- Kenny PJ, Chartoff E, Roberto M, Carlezon WA, Markou A. NMDA Receptors Regulate Nicotine-Enhanced Brain Reward Function and Intravenous Nicotine Self-Administration: Role of the Ventral Tegmental Area and Central Nucleus of the Amygdala. Neuropsychopharmacology. 2009;34(2):266-281.
- Chartoff EH, Papadopolou M, Macdonald ML, Parsegian A, Potter D, Konradi CL, Carlezon WA. Desipramine reduces stress-activated dynorphin expression and CREB phosphorylation in NAc tissue. Mol Pharmacol. 2009;75(3):704-712.
- Ebner SR, Roitman MF, Potter DN, Rachlin AB, Chartoff EH. Depressive-like effects of the kappa opioid receptor agonist salvinorin A are associated with decreased phasic dopamine release in the nucleus accumbens. Psychopharmacology. 2010 Jun;210(2):241-52.PMID: 20372879.
- Potter DN, Damez-Werno D, Carlezon WA Jr., Cohen BM, Chartoff EH. Repeated exposure to the kappa- opioid receptor agonist salvinorin A modulates extracellular signal regulated kinase and reward sensitivity. Biological Psychiatry. 2011. Jul. PMID: 21757186
- Chartoff EH, Sawyer A, Rachlin A, Potter D, Pliakas A, Carlezon WA Jr. Blockade of kappa-opioid receptors attenuates the development of depressive-like behaviors induced by cocaine withdrawal in rats. Neuropharmacology. 2011. Jun. PubMed: 21736885.
