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Meet Our Florida Scientists Jay McLaughlin
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Jay McLaughlin

Jay McLaughlinTorreyPinesInstituteFL

Associate Member
Pharmacology and Neuroscience

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Dr. McLaughlin’s research is focused on pain management.  Specifically, he is examining the neurobiological basis of behavior, focusing on the molecular, pharmacological and neurological mechanisms underlying behavioral and psychological disorders. Since establishing his own laboratory, his work has examined the interactions of stress-induced endogenous opioids (e.g., endorphins and dynorphins) and hormones with reward pathways, and the resultant behavioral consequences in animal models of mood disorders, learning and memory, and drug abuse.  Molecular, pharmacological, anatomical and behavioral methodologies are utilized.

Current behavioral research focuses on how stress-induced release of various neurotransmitters and hormones mediates anxiety, depression and drug abuse, as well as learning and memory performance.  Concurrently, neuroanatomical examination to determine the brain regions involved in these behaviors is underway, utilizing both immunochemical methods to examine activated signal transduction pathways and live imaging to examine functional changes and integrity of related brain circuitry.  Pharmacological studies examine novel opioid compounds as both low-liability analgesics and as therapeutics for drug abuse.  Finally, molecular neurobiological research focuses on the regulatory systems controlling opioid and dopamine neurotransmitter receptors and transporters, and how hormones released in response to stress alter the function of these systems. The overall goal of Dr. McLaughlin’s research is to identify the neurotransmitter systems underlying these behaviors, characterize them, and develop new therapeutic treatments.

Dr. McLaughlin’s research is aimed at examining the neurobiological basis of behavior, focusing on the molecular, pharmacological and neurological mechanisms underlying behavior and psychological disorders. Since establishing his own laboratory, he has examined the interactions of stress-induced endogenous opioids (e.g., endorphins and dynorphins) and hormones with reward pathways, and the resultant behavioral consequences in animal models of mood disorders, learning and memory, and drug abuse.  Molecular, pharmacological, anatomical and behavioral methodologies are used. Current behavioral research focuses on how stress-induced release of various neurotransmitters and hormones mediates anxiety, depression and drug abuse, as well as learning and memory performance.  Concurrently, neuroanatomical examination to determine the brain regions involved in these behaviors is underway, utilizing both immunochemical methods to examine activated signal transduction pathways and live imaging to examine functional changes and integrity of related brain circuitry.  Pharmacological studies examine novel opioid compounds as both low-liability analgesics and as therapeutics for drug abuse.  Finally, molecular neurobiological research focuses on the regulatory systems controlling opioid and dopamine neurotransmitter receptors and transporters, and how hormones released in response to stress alter the function of these systems. The overall goal of Dr. McLaughlin’s research is to identify the neurotransmitter systems underlying these behaviors, characterize them, and develop new therapeutic interventions.

Presently, the lab is organized around five major on-going research projects:

  • Screening of novel opioid compounds as analgesics and therapeutics in drug abuse.  Growing out of this first body of work, this project has two components.  First, we are examining the in vivo analgesic activity of opioid ligands synthesized from a combinatorial chemistry library and provided by the Torrey Pines Institute.  While this research is ongoing, we have already identified a systemically active opioid agonist that is long lasting, producing dose-dependent analgesia for over 8 hours and with a potency five-fold greater than morphine, but lacking the liabilities (respiratory depression and reinforcing properties) of morphine.   Second, we are screening peptide kappa opioid agonists and antagonists as therapeutics for cocaine abuse, examining compounds synthesized by the lab of Dr. Jane Aldrich.  Again, this work is ongoing, but we have already identified a systemically active peptide antagonist that crosses the blood-brain barrier to suppress the stress-induced reinstatement of cocaine-conditioned place preference, demonstrating potential future therapeutic value
  • Mechanisms by which stress modulates reward and contributes to disorders of mood, drug abuse, learning and memory.  This project has demonstrated that exposure to stress activates the endogenous kappa opioid system to potentiate reward and induce relapse to extinguished drug-seeking (cocaine and ethanol) behaviors, as well as increase depression-like behaviors and impede learning and memory behaviors.  Present findings suggest that novel kappa opioid agonists may be beneficial in the short term to prevent acute narcotic-induced reward, but that antagonists may be of additional benefit as treatments for drug relapse and antidepressants.  We have demonstrated that kappa-opioid receptor stimulation is necessary and sufficient to produce the potentiation.  We have further traced the mechanism of potentiation to the activation of mitogen activated protein (MAP) kinases.  This is significant, given the integrative role MAP kinase plays in controlling diverse signaling events through the cell, with the ability to both alter the operation of existing proteins as well as induce expression of new proteins. Additionally, we have preliminary evidence demonstrating that earlier exposure to stress increases drug-seeking and depression-like behaviors for extended (weeks) periods in mice, an animal model of PTSD.  Importantly, we have demonstrated novel pharmacological strategies to reverse this effect after the fact.
  • Mechanisms by which pain and inflammation mediate opioid reward.  Following a related theme to the research on stress, our initial findings have demonstrated a similar role for the hormone interleukin-1β on drug reward.  The interleukins are hormones released in response to pain, stress or inflammation, and have also been demonstrated to modulate morphine reward in a time dependent manner.  Acute and prolonged treatment with interleukin-1β suppresses both the analgesic and rewarding effects of morphine, mimicking the effects of exposure to either prolonged stress or inflammatory injury.  However, cessation of interleukin-1β treatment results in a dramatic increase in morphine reward.  This suggests for the first time a biological agent linking inflammation, stress and opioid reward, a significant concern given the explosion of prescription opioid abuse in the United States.  We will continue to characterize this relationship in the next year, further examining the reinstating capabilities demonstrated by administration of interleukin-1β to mice demonstrating extinction of morphine conditioned place preference.
  • Mechanisms by which HIV alters related behavior.  The widespread use of HAART therapies has curtailed the expression and spread of the Human Immunodeficiency Virus, but these patients continue to display severe behavioral disorders that cannot be presently accounted for, a syndrome roughly defined as NeuroAIDS.  This project examines the contribution of the HIV-accessory protein, Tat, to the development of NeuroAIDS-related behaviors in an animal model. To date, we have demonstrated that expression of the Tat protein is sufficient to produce the NeuroAIDS-related increases in drug seeking and anxiety-related behaviors, as well as deficits in learning and memory performance.  Recent work is further examining the effects of Tat on depression-like as well as cognitive function.  Moreover, collaborative efforts with the research group of Dr. Marc Kaufman at McLean Hospital are utilizing fMRI techniques to correlate observed behavioral changes with alterations in the integrity and function of related neuroanatomical circuits.  While Tat protein is known to exert neurodegenerative effects at high doses, the effect of Tat expression on overall neurological function prior to cell death is not known, but of great interest to the HIV-AIDS community.  It is hoped this effort will shed light on the neurological response made by the organism to HIV-infection.  Curiously, we have also recently demonstrated that Tat protein promotes MAP kinase activity to induce behavioral deficits, suggesting new therapeutic approaches in the treatment of NeuroAIDS may be both possible and testable in this model.
  • Mechanisms of abused drugs and opioid signaling.   This basic science project draws from the results of the first two projects.  We are examining the control of the MAP kinases by the opioid receptor, and the impact such regulation may have on additional proteins of importance to signaling drug reward and depression, specifically, the dopamine transporter.  Recent evidence demonstrates an agonist-specific, kappa opioid receptor mediated activation of MAP kinase that paradoxically produces a potentiation of drug reward.  As this is agonist specific, we are presently screening novel kappa agonists that do not activate MAP kinase as improved therapeutics for drug abuse.  Moreover, very recent research has suggested for the first time that selected kappa opioid receptor antagonists may act as inverse agonists, reversing the activation of MAP kinase.  If confirmed, this result may both add to our understanding of opioid pharmacology, and also provide a completely new approach in the treatment of behavioral disorders associated with MAP kinase activity, such as relapse to drug abuse and mood disorders.

 

Dr. Jay P. McLaughlin earned his Bachelor of Arts in Biology from the University of California at Santa Cruz in 1989.  Upon completion of his undergraduate degree, he was employed as a Research Technician at the cardiology laboratory of Robert Marshall at the Veteran Affairs Hospital in Martinez, California, until July of 1991.  From January 1991 until June of 1992, he worked as a Production Technician at Genentech, Inc., in South San Francisco, California.  Dr. McLaughlin received a Master of Science in Neuroscience degree in 1996 and a PhD in Neuroscience degree in 1998, both from the University of Rochester School of Medicine and Dentistry in Rochester, New York.  Following his doctoral studies, he held two postdoctoral fellow positions, one at the University of Rochester from 1998 to 1999 and the other at the University of Washington, Seattle, Washington, from 1999 to 2002.  From early 2002 until October of 2003, he served as an Acting Instructor at the University of Washington and then assumed the position of Acting Assistant Professor there from October 2003 until August of 2004.  At that time, Dr. McLaughlin became an Assistant Professor at Northeastern University in Boston, Massachusetts, where he remained until June of 2010.  He joined Torrey Pines Institute of Molecular Studies in Port St. Lucie, Florida, as an Associate Member in February 2009.

Education

  • 1998 - Doctor of Philosophy (Neuroscience). University of Rochester, School of Medicine and Dentistry, Rochester, NY
  • 1996 - Master of Science (Neuroscience). University of Rochester, School of Medicine and Dentistry, Rochester, NY
  • 1989 - Bachelor of Arts (Biology). University of California at Santa Cruz, Santa Cruz, California

Positions

  • 2009 – Present, Associate Member, Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida
  • 2004 – 2010, Assistant Professor, Northeastern University, Boston, Massachusetts
  • 2003 – 2004, Acting Assistant Professor, University of Washington, Seattle, Washington
  • 2002 – 2003, Acting Instructor, University of Washington, Seattle, Washington
  • 1999 - 2002, Postdoctoral Fellow, University of Washington, Seattle, Washington
  • 1991 – 1992, Production Technician, Genentech, Inc., South San Francisco, California
  • 1989 – 1991, Research Technician, Cardiology laboratory of Robert Marshall, Veteran Affairs Hospital, Martinez, California

Professional Affiliations

  • Full Member, Society for Neuroscience
  • Member, International Narcotics Research Conference
  • Reviewer, NIDA B/START program
  • Member, College on Problems of Drug Dependence

Honors & Awards

  • Invited speaker, Brain Research Week, Moravian College, 2008
  • Teaching Excellence Award, Department of Psychology, Northeastern University, 2007
  • Recipient, NIDA Director’s Travel Award to attend the College on Problems of Drug Dependence meeting in Scottsdale, Arizona, 1995 and 1998
  • Travel Fellowship to attend and present research at International Narcotics Research Conferences, 1994, 1998, 2001, 2002, 2003, 2005, 2006, 2008 and 2009

Selected Publications (10 of 28)

  1. McLaughlin, J.P., Hill, K.P., Jiang, Q., Sebastian, A., Archer, S. and Bidlack, J.M.: Nitrocinnamoyl and chlorocinnamoyl derivatives of dihydrocodeinone: In vivo and in vitro characterization of µ-selective opioid agonist and antagonist activity. J. Pharmacol. Exp. Ther., 289: 304-311, 1999.
  2. Xie, W., Samoriski, G.M., McLaughlin, J.P., Rosomer, V., Smrcka, A., Hinkle, P.M., Bidlack, J.M., Gross, R.A., Jiang, H. and Wu, D.: Genetic alteration of PLCß3 expression modulates behavioral and cellular responses to opioids. Proc. Natl. Acad. Sci. USA., 96: 10385-10390, 1999.
  3. McLaughlin, J.P. and Chavkin, C.: Tyrosine phosphorylation of the mu opioid receptor regulates agonist intrinsic efficacy.  Mol. Pharmacol., 59: 1360-1368, 2001.
  4. McLaughlin, J.P., Marton-Popovici M. and Chavkin, C.: Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses.  J. Neurosci. 23: 5674-5683, 2003.
  5. McLaughlin, J.P., Myers, L.C., Zarek, P.E., Caron M.G., Lefkowitz R.J., Czyzyk T.A., Pintar J.E. and Chavkin, C.: Prolonged kappa-opioid receptor phosphorylation mediated by G-protein receptor kinase underlies sustained analgesic tolerance.  J. Biol. Chem., 279: 1810-1818, 2004.
  6. McLaughlin, J.P., Land, B.B., Li, S., Pintar, J.E. and Chavkin, C.: Prior activation of kappa opioid receptors by U50,488 mimics repeated forced swim stress to potentiate cocaine place preference conditioning.  Neuropsychopharmacology, 31: 787-794, 2006.
  7. Carey A.N., Borozny K., Aldrich J.V. and McLaughlin J.P.: Reinstatement of cocaine place-conditioning prevented by the peptide kappa-opioid receptor antagonist arodyn. European Journal of Pharmacology, 569: 84-89, 2007.
  8. Carey A.N., Lyons A.M., Shay C.F., Dunton O. and McLaughlin J.P.: Endogenous kappa opioid activation mediates stress-induced deficits in learning and memory. Journal of Neuroscience,29:4293-4300, 2009.
  9. Aldrich J.V., Patkar K.A. and McLaughlin J.P.: Zyklophin, a systemically active selective kappa opioid receptor peptide antagonist.  Proceedings of the National Academy of Science, USA, 106:18396-18401, 2009.
  10. Sperling R.E., Gomes S.M., Sypek E.I., Carey A.N. and McLaughlin J.P.: Endogenous kappa opioid mediation of stress-induced potentiation of ethanol conditioned place preference and self administration.  Psychopharmacology, 210(2):199-209, 2010.