Jay McLaughlin

Jay McLaughlin, Ph.D.


Department: Pharmacodynamics
Business Phone: (352) 273-7207
Business Email: jmclaughlin@cop.ufl.edu

About Jay McLaughlin

Jay McLaughlin, Ph.D., joined the College of Pharmacy as an associate professor of pharmacodynamics and was promoted to professor in July 2020. Prior to joining UF, he worked at the Torrey Pines Institute for Molecular Studies in Port St. Lucie, Florida. His research goal is to identify the neurobiological systems underlying behavior, characterizing them and related psychological disorders to developing new therapeutic interventions utilizing molecular, pharmacological, anatomical and behavioral methods. His projects encompass both basic science and drug discovery elements.


Preeminence Faculty Member
2015-Current · University of Florida
Travel Fellowship
2008-2009 · International Narcotics Research Conference
Teaching Excellence Award
2007 · Northeastern University
Travel Fellowship
2006 · International Narcotics Research Conference
Travel Fellowship
2005 · International Narcotics Research Conference
Travel Fellowship
2001-2003 · International Narcotics Research Conference
Travel Fellowship
1998 · International Narcotics Research Conference
NIDA Director’s Travel Award
1998 · College on Problems of Drug Dependence Meeting
NIDA Director’s Travel Award
1995 · College on Problems of Drug Dependence Meeting
Travel Fellowship
1994 · International Narcotics Research Conference

Research Profile

I am interested in questions examining the neurobiological basis of behavior, focusing on the molecular, pharmacological and neurological mechanisms underlying behavior and psychological disorders. While these interests are broad, my overall goal is to identify the neurobiological systems underlying these behaviors, characterize them, and develop new therapeutic interventions. Working towards this goal, I utilize molecular, chemical, pharmacological, anatomical and behavioral methodology. Ongoing projects include:

Mechanisms by which HIV mediates neuropathology and alters behavior. The widespread use of HAART therapies has curtailed the expression and spread of the Human Immunodeficiency Virus (Cohen et al., 2011), but these patients continue to display severe neuropathology and behavioral disorders that cannot be presently accounted for including deficits in motor coordination, learning and memory, behavioral inhibition, and affective well-being (Woods et al. 2009), a syndrome roughly defined as NeuroAIDS. The HIV regulatory protein, Tat, has been implicated in the pathogenesis of HIV-1 neurological complications (Rappaport et al., 1999), but direct demonstrations of the effects of Tat on behavior and neurodegeneration in an intact organism in vivo are limited. This project used for the first time a novel animal model, the GT-tg bigenic mouse. These mice contain a doxycycline (Dox)-inducible and brain-selective tat gene coding for Tat protein, allowing the controlled expression of Tat protein for selective study on desired pathological and behavioral questions. Accordingly, this project uses GT-tg bigenic mice to test the hypothesis that the activity of Tat in brain is sufficient to produce neuronal dysfunction and neurodegeneration producing behavioral deficits in learning and memory performance, mood disorders, and increases in drug seeking behaviors.

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.Additional work under this project has also demonstrated that endogenous kappa opioid activation mediates stress-induced deficits in learning and memory (Carey et al., J Neurosci. 29:4293-4300, 2009). Overall, these results suggest that stress-induced activation of the KOR may be both necessary and sufficient to produce subsequent deficits in novel object recognition, and suggest both new insights into the means by which stress impairs learning and memory performance, as well as therapeutic approaches for treating exposure to stress.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. 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 recently demonstrated novel pharmacological strategies to reverse this effect after the fact (Hymel et al., Behav Pharmacol, 25:599-608, 2014).

Screening of novel compounds as analgesics and therapeutics for drug abuse. This translational project has multiple components. First, we are screening peptide kappa opioid agonists and antagonists as therapeutics for cocaine abuse, examining compounds synthesized by the lab of Dr. Jane Aldrich. This work is ongoing, but we have already identified a systemically active peptide antagonist, zyklophin, that crosses the blood-brain barrier to suppress the stress-induced reinstatement of cocaine-conditioned place preference (Aldrich et al., Proc Natl. Acad Sci, USA, 106:18396-18401, 2009). In a recent extension of this research funded from NIH-NIDA (R01 DA018832-06 and R01 DA023924-06), we have identified a set of cyclic tetrapeptides which may have promise as both analgesics and therapeutics for drug abuse. The lead compounds in this series have demonstrated both mixed opioid-receptor agonism and kappa-opioid receptor antagonism (Ross et al., British Journal of Pharmacology, 165(4b):1097-1108, 2012), and after oral administration have proven effective in preventing both the acutely rewarding effects of cocaine and prevents both stress and drug-induced reinstatement of extinguished drug-seeking behavior (Aldrich et al., Journal of Natural Products, 76(3):433-438, 2013 and Eans et al., British Journal of Pharmacology, 169(2):426-436, 2013). New compounds arising from this series show greater efficacy in opioid activity while preventing relapse to extinguished cocaine-seeking behavior, and in recent tests, morphine-seeking behavior. These findings support the purpose of a recent project funded by the DoD (PR141230) to seek therapeutics for abuse of a broad range of psychostimulants.An additional collaboration seeking novel analgesics is currently underway with Dr. Chris McCurdy at the University of Mississippi. This collaboration has produced two lines of research. In the first, my lab is characterizing a novel sigma ligand for analgesic properties, recently finding that this lead compound relieves neuropathic pain without addictive properties or sedative effects. This work contributed justification for the first clinical trial in February, 2016 where a radiolabeled version of the lead compound was found to image the site of neuropathic injury. In a second project recently funded by NIDA (R01 DA034777), we are developing a series of small molecule guanidine-piperdines agonists and antagonists selective for neuropeptide FF (NPFF)-receptor subtypes. The lead compound in this project has been recently characterized as an NPFF-1 receptor antagonist (Journigan et al., Journal of Medicinal Chemistry, 57(21):8903-8927, 2014), and shown since to prevent acute morphine antinociceptive tolerance. In a continuation of this work, we are screening ligands with dual opioid- and NPFF-receptor activity. To date, we have identified a lead compound demonstrating mixed opioid agonism and NPFF-receptor antagonism which produce potent analgesia without tolerance.


Apr 2020 ACTIVE
Synthesis and in vitro and in vivo screening of fused and tethered heterocyclic peptidomimetics for the discovery of new analgesics with decreased side effects
Apr 2018 ACTIVE
Molecular mechanisms: Dysregulation of monoamine transporters by HIV-1 Tat and cocaine.
UNIV OF SOUTH CAROLINA · Principal Investigator
Sep 2017 ACTIVE
Sigma receptor ligands as non-opioid based pain management.
US ARMY MED RES ACQUISITION · Principal Investigator
Apr 2017 – Aug 2019
Optimization of non-peptide probes for the NPFF receptor system
Sep 2016 – Feb 2019
Novel Opioid Peptides for Nose to Brain Delivery
FL ATLANTIC UNIV · Principal Investigator
Jun 2016 – May 2019
Knock-in mouse model of dopamine transporter-Tat Interaction underlying NeuroAIDS
UNIV OF SOUTH CAROLINA · Principal Investigator
Sep 2015 – Aug 2017
Optimization of non-peptide probes for the NPFF Receptor system
UNIV OF MISSISSIPPI · Principal Investigator
Sep 2015 – Aug 2019
Novel peptide antagonists as treatments for substance abuse
US ARMY MED RES ACQUISITION · Principal Investigator
Aug 2015 ACTIVE
HIV Tat protein mediation of neurochemical changes and increased opioid reward
NATL INST OF HLTH NIDA · Principal Investigator
May 2015 – Oct 2017
Tat mediation of HIV-associated mood disorders via
NATL INST OF HLTH NIMH · Principal Investigator
Apr 2015 ACTIVE
Peptidic Kappa Opioid Receptor Ligands as Potential Treatments for Drug Addiction
NATL INST OF HLTH NIDA · Project Manager
Mar 2015 – Feb 2018
Peptidic Ligands for Kappa Opioid Receptors
NATL INST OF HLTH NIDA · Project Manager


Ph.D. – Neuroscience
1998 · University of Rochester
M. S. – Neuroscience
1996 · University of Rochester
B.A. – Biology
1989 · University of California at Santa Cruz

Contact Details

(352) 273-7207