Jay McLaughlin

Jay McLaughlin, Ph.D.

Professor

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.

Accomplishments

Team Teaching Award (PC6 ALS1)
2020 · University of Florida, College of Pharmacy
Term Professor
2019-2022 · University of Florida
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.

Open Researcher and Contributor ID (ORCID)

0000-0001-9851-9342

Publications

2021
Kratom Alkaloids, Natural and Semi-Synthetic, Show Less Physical Dependence and Ameliorate Opioid Withdrawal.
Cellular and molecular neurobiology. [DOI] 10.1007/s10571-020-01034-7. [PMID] 33433723.
2020
Chronic Voluntary Binge Ethanol Consumption Causes Sex-Specific Differences in Microglial Signaling Pathways and Withdrawal-associated Behaviors in Mice.
Alcoholism, clinical and experimental research. 44(9):1791-1806 [DOI] 10.1111/acer.14420. [PMID] 32767774.
2020
Design, Synthesis, and Characterization of the Macrocyclic Tetrapeptide cyclo[Pro-Sar-Phe-d-Phe]: A Mixed Opioid Receptor Agonist-Antagonist Following Oral Administration.
ACS chemical neuroscience. 11(9):1324-1336 [DOI] 10.1021/acschemneuro.0c00086. [PMID] 32251585.
2020
Discovery of a Highly Selective Sigma-2 Receptor Ligand, 1-(4-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one (CM398), with Drug-Like Properties and Antinociceptive Effects In Vivo.
The AAPS journal. 22(5) [DOI] 10.1208/s12248-020-00472-x. [PMID] 32691179.
2020
HIV-1 Tat and cocaine impact mitochondrial epigenetics: effects on DNA methylation.
Epigenetics. 1-20 [DOI] 10.1080/15592294.2020.1834919. [PMID] 33100130.
2020
HIV-Tat and Cocaine Impact Brain Energy Metabolism: Redox Modification and Mitochondrial Biogenesis Influence NRF Transcription-Mediated Neurodegeneration.
Molecular neurobiology. [DOI] 10.1007/s12035-020-02131-w. [PMID] 32978730.
2020
Lyophilized Kratom Tea as a Therapeutic Option for Opioid Dependence.
Drug and alcohol dependence. 216 [DOI] 10.1016/j.drugalcdep.2020.108310. [PMID] 33017752.
2020
Multifunctional opioid receptor agonism and antagonism by a novel macrocyclic tetrapeptide prevents reinstatement of morphine-seeking behaviour.
British journal of pharmacology. 177(18):4209-4222 [DOI] 10.1111/bph.15165. [PMID] 32562259.
2020
Phenylalanine Stereoisomers of CJ-15,208 and [d-Trp]CJ-15,208 Exhibit Distinctly Different Opioid Activity Profiles.
Molecules (Basel, Switzerland). 25(17) [DOI] 10.3390/molecules25173999. [PMID] 32887303.
2020
Preventing Morphine-Seeking Behavior through the Re-Engineering of Vincamine’s Biological Activity.
Journal of medicinal chemistry. 63(10):5119-5138 [DOI] 10.1021/acs.jmedchem.9b01924. [PMID] 31913038.
2020
[3H]Dopamine Uptake through the Dopamine and Norepinephrine Transporters is Decreased in the Prefrontal Cortex of Transgenic Mice Expressing HIV-1 Transactivator of Transcription Protein.
The Journal of pharmacology and experimental therapeutics. 374(2):241-251 [DOI] 10.1124/jpet.120.266023. [PMID] 32461322.
2020
Region-specific effects of HIV-1 Tat on intrinsic electrophysiological properties of pyramidal neurons in mouse prefrontal cortex and hippocampus.
Journal of neurophysiology. 123(4):1332-1341 [DOI] 10.1152/jn.00029.2020. [PMID] 32101482.
2019
Characterization of Sigma 1 Receptor Antagonist CM-304 and Its Analog, AZ-66: Novel Therapeutics Against Allodynia and Induced Pain.
Frontiers in pharmacology. 10 [DOI] 10.3389/fphar.2019.00678. [PMID] 31258480.
2019
Antinociceptive activity of thiazole-containing cyclized DAMGO and Leu-(Met) enkephalin analogs.
Organic & biomolecular chemistry. 17(21):5305-5315 [DOI] 10.1039/c9ob00882a. [PMID] 31094391.
2018
A stable isotope dilution tandem mass spectrometry method of major kavalactones and its applications.
PloS one. 13(5) [DOI] 10.1371/journal.pone.0197940. [PMID] 29795658.
2018
HIV-1 Tat regulation of dopamine transmission and microglial reactivity is brain region specific.
Glia. 66(9):1915-1928 [DOI] 10.1002/glia.23447. [PMID] 29733459.
2017
A one-pot multicomponent approach to a new series of morphine derivatives and their biological evaluation.
Organic & biomolecular chemistry. 15(37):7796-7801 [DOI] 10.1039/c7ob01924f. [PMID] 28875208.
2017
Conditional Human Immunodeficiency Virus Transactivator of Transcription Protein Expression Induces Depression-like Effects and Oxidative Stress.
Biological psychiatry. Cognitive neuroscience and neuroimaging. 2(7):599-609 [DOI] 10.1016/j.bpsc.2017.04.002. [PMID] 29057370.
2017
Selective κ receptor partial agonist HS666 produces potent antinociception without inducing aversion after i.c.v. administration in mice.
British journal of pharmacology. 174(15):2444-2456 [DOI] 10.1111/bph.13854. [PMID] 28494108.
2016
Altered Secondary Structure of Dynorphin a Associates With Loss of Opioid Signalling and Nmda-Mediated Excitotoxicity in Sca23
Human Molecular Genetics. 25(13):2728-2737 [DOI] 10.1093/hmg/ddw130.
2016
Direct Phenotypic Screening in Mice: Identification of Individual, Novel Antinociceptive Compounds from a Library of 734,821 Pyrrolidine Bis-piperazines.
ACS combinatorial science. 18(1):51-64 [DOI] 10.1021/acscombsci.5b00126. [PMID] 26651386.
2016
Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2.
Journal of medicinal chemistry. 59(18):8381-97 [DOI] 10.1021/acs.jmedchem.6b00748. [PMID] 27556704.

Grants

Sep 2020 ACTIVE
Therapeutic and mechanistic evaluation of multifunctional opioids as improved treatments for pain and substance abuse
Role: Other
Funding: AMER FOU FOR PHARM EDU
Sep 2020 ACTIVE
Pharmacological probes based on mitragynine pseudoindoxyl.
Role: Principal Investigator
Funding: ST LOUIS COLLEGE OF PHARMACY via NATL INST OF HLTH NIDA
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
Role: Principal Investigator
Funding: FLORIDA INTERNATIONAL UNIV via NATL INST OF HLTH NIDA
Apr 2018 ACTIVE
Molecular mechanisms: Dysregulation of monoamine transporters by HIV-1 Tat and cocaine.
Role: Principal Investigator
Funding: UNIV OF SOUTH CAROLINA via NATL INST OF HLTH NIDA
Sep 2017 ACTIVE
Sigma receptor ligands as non-opioid based pain management.
Role: Principal Investigator
Funding: US ARMY MED RES ACQUISITION
Apr 2017 – Aug 2019
Optimization of non-peptide probes for the NPFF receptor system
Role: Co-Investigator
Funding: NATL INST OF HLTH NIDA
Sep 2016 – Feb 2019
Novel Opioid Peptides for Nose to Brain Delivery
Role: Principal Investigator
Funding: FL ATLANTIC UNIV via NATL INST OF HLTH NIDA
Jun 2016 – May 2019
Knock-in mouse model of dopamine transporter-Tat Interaction underlying NeuroAIDS
Role: Principal Investigator
Funding: UNIV OF SOUTH CAROLINA via NATL INST OF HLTH NIDA
Sep 2015 – Aug 2017
Optimization of non-peptide probes for the NPFF Receptor system
Role: Principal Investigator
Funding: UNIV OF MISSISSIPPI via NATL INST OF HLTH
Sep 2015 – Aug 2019
Novel peptide antagonists as treatments for substance abuse
Role: Principal Investigator
Funding: US ARMY MED RES ACQUISITION
Aug 2015 ACTIVE
HIV Tat protein mediation of neurochemical changes and increased opioid reward
Role: Principal Investigator
Funding: NATL INST OF HLTH NIDA
May 2015 – Oct 2017
Tat mediation of HIV-associated mood disorders via
Role: Principal Investigator
Funding: NATL INST OF HLTH NIMH
Apr 2015 ACTIVE
Peptidic Kappa Opioid Receptor Ligands as Potential Treatments for Drug Addiction
Role: Project Manager
Funding: NATL INST OF HLTH NIDA
Mar 2015 – Feb 2018
Peptidic Ligands for Kappa Opioid Receptors
Role: Project Manager
Funding: NATL INST OF HLTH NIDA

Education

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

Teaching Profile

Courses Taught
2017-2018,2020
PHA5788C Patient Care 6
2016-2017,2019-2021
PHA6521C Research Techniques in Pharmacodynamics
2016-2021
PHA7980 Research for Doctoral Dissertation
2016-2021
PHA7979 Advanced Research
2016-2017,2020-2021
PHA6936 Advanced Topics in Pharmaceutical Sciences
2016-2021
PHA6512L Experiential Research Training in Pharmacodynamics
2019-2020
PHA6910 Supervised Research
2019-2020
PHA6935 Selected Topics in Pharmacy
2020
PHA6971 Research for Master’s Thesis
2016-2019
PHA5561 Pathphys-Pt Assess II
2017-2018
PHA4911 Undergraduate Research in Pharmacodynamics
2016
PHA5517 Pharmacol Bas Ther 2
2016
GMS7794 Neuroscience Seminar
2015
PHA5902 Research Pharmacodyna
2015
PHA5561C Physiol Bas Disease 2
2021
BSC4910 Individual Mentored Research in Biology

Contact Details

Phones:
Business:
(352) 273-7207
Emails: