Jay McLaughlin
Assistant Professor
125 Nightingale
(617) 373-2361 (office)
(617) 373-8714 (fax)
j.mclaughlin@neu.edu

• See curriculum vitae (pdf)

Research

The McLaughlin lab is interested in questions examining the neurobiological basis of behavior, focusing on the molecular, pharmacological and neurological mechanisms underlying behavior and psychological disorders. Research since arriving at Northeastern 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. Presently, the lab is organized around five major on-going research projects:

• 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 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.  Interestingly, 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.
• 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 peptide library and provided by the Torrey Pines Institute.  While this research is ongoing, we have already identified a systemically active peptide agonist that is long lasting, producing dose-dependent analgesia for over 8 hours and with a potency five-fold greater than 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 at the University of Kansas.  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 pain and inflammation mediate opioid reward.  Following a related theme to the research on stress, initial findings in my lab have demonstrated a similar role for the hormone interleukin-1b 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-1b 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-1b 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, further examining the reinstating capabilities demonstrated by administration of interleukin-1b 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 can not 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 are using 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.
• Mechanisms of signaling by abused drugs and other opioids.   Drawing 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 in fact 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.

Frequently Taught Courses

PSYC 4656: Seminar in Psychobiology (fall)
PSYC 4606: Laboratory in Psychobiology (spring)