Edward Levin

Overview:

Dr. Levin is Chief of the Neurobehavioral Research Lab in the Psychiatry Department of Duke University Medical Center. His primary academic appointment is as Professor in the Department of Psychiatry and Behavioral Sciences. He also has secondary appointments in the Department Pharmacology and Cancer Biology, the Department of Psychological and Brain Sciences and the Nicholas School of the Environment at Duke. His primary research effort is to understand basic neural interactions underlying cognitive function and addiction and to apply this knowledge to better understand cognitive dysfunction and addiction disorders and to develop novel therapeutic treatments.

The three main research components of his laboratory are focused on the themes of the basic neurobiology of cognition and addiction, neurobehavioral toxicology and the development of novel therapeutic treatments for cognitive dysfunction and substance abuse. Currently, our principal research focus concerns nicotine. We have documented the basic effects of nicotine on learningm memory and attention as well as nicotine self-administration. We are continuing with more mechanistic studies in rat models using selective lesions, local infusions and neurotransmitter interaction studies. We have found that nicotine improves memory performance not only in normal rats, but also in rats with lesions of hippocampal and basal forebrain connections. We are concentrating on alpha7 and alpha4beta2 nicotinic receptor subtypes in the hippocampus, amygdala , thalamus and frontal cortex and how they interact with dopamine D1 and D2 and glutamate NMDA systems with regard to memory and addiction. I am also conducting studies on human cognitive behavior. We have current studies to assess nicotine effects on attention, memory and mental processing speed in schizophrenics, Alzheimer's Disease patients and people with Attention Deficit Hyperactivity Disorder. In the area of neurobehavioral toxicology, I have continuing projects to characterize the adverse effects of prenatal and adolescent nicotine exposure. Our primary project in neurobehavioral toxicology focuses on the cognitive deficits caused by the marine toxins including domoic acid, ciguatera toxin and pfiesteria. We have documented a persistent neurobehavioral effects caused by Pfiesteria and domoic acid exposure. We are determining the neurobehavioral nature and mechanisms of this deficit. The basic and applied aims of our research complement each other nicely. The findings concerning neural mechanisms underlying cognitive function help direct the behavioral toxicology and therapeutic development studies, while the applied studies provide important functional information concerning the importance of the basic mechanisms under investigation.

Positions:

Professor in Psychiatry and Behavioral Sciences

Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences
School of Medicine

Director, Integrated Toxicology Program

School of Medicine
School of Medicine

Professor in the Environmental Sciences and Policy Division

Environmental Sciences and Policy
Nicholas School of the Environment

Associate Professor of Pharmacology & Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Professor of Psychology and Neuroscience

Psychology and Neuroscience
Trinity College of Arts & Sciences

Faculty Network Member of the Duke Institute for Brain Sciences

Duke Institute for Brain Sciences
Institutes and Provost's Academic Units

Affiliate of the Duke Initiative for Science & Society

Duke Science & Society
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1984

University of Wisconsin - Madison

Grants:

Alzheimer's Disease, Genes, and Pesticide Use in the Agricultural Health Study

Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Study of Novel Treatment to Prevent Acquisition of Opiate Self-Administration in Rats

Administered By
Psychiatry & Behavioral Sciences
Awarded By
Amygdala Neurosciences Inc.
Role
Co Investigator
Start Date
End Date

Advancing Mechanistic Understanding of Neurotoxic Contributors to Autism

Administered By
Psychiatry & Behavioral Sciences
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Establishing an AOP for the Role of the Vitamin D Receptor in Developmental Neurotoxicity

Administered By
Psychiatry & Behavioral Sciences
Awarded By
North Carolina State University
Role
Principal Investigator
Start Date
End Date

Screening for Potential Persisting Neurobehavioral Effects in Zebrafish following Developmental Exposure to Classes of Compounds: Flame Retardants, A Case Example

Administered By
Psychiatry & Behavioral Sciences
Awarded By
National Institute of Environmental Health Sciences
Role
Principal Investigator
Start Date
End Date

Publications:

Refraining from use diminishes cannabis-associated epigenetic changes in human sperm.

Cannabis use alters sperm DNA methylation, but the potential reversibility of these changes is unknown. Semen samples from cannabis users and non-user controls were collected at baseline and again following a 77-day period of cannabis abstinence (one spermatogenic cycle). Users and controls did not significantly differ by demographics or semen analyses. Whole-genome bisulfite sequencing identified 163 CpG sites with significantly different DNA methylation in sperm between groups (P < 2.94 × 10-9). Genes associated with altered CpG sites were enriched with those involved in development, including cardiogenesis and neurodevelopment. Many of the differences in sperm DNA methylation between groups were diminished after cannabis abstinence. These results indicate that sustained cannabis abstinence significantly reduces the number of sperm showing cannabis-associated alterations at genes important for early development.
Authors
Schrott, R; Murphy, SK; Modliszewski, JL; King, DE; Hill, B; Itchon-Ramos, N; Raburn, D; Price, T; Levin, ED; Vandrey, R; Corcoran, DL; Kollins, SH; Mitchell, JT
MLA Citation
Schrott, Rose, et al. “Refraining from use diminishes cannabis-associated epigenetic changes in human sperm.Environ Epigenet, vol. 7, no. 1, 2021, p. dvab009. Pubmed, doi:10.1093/eep/dvab009.
URI
https://scholars.duke.edu/individual/pub1497117
PMID
34557312
Source
pubmed
Published In
Environmental Epigenetics
Volume
7
Published Date
Start Page
dvab009
DOI
10.1093/eep/dvab009

Risk for opioid abuse is diminished by inhibiting aldehyde dehydrogenase-2 (ALDH-2) in rats

Significant opiate addiction is known to follow prescribed opiate use for pain. There is a serious unmet need for non-addicting medications to prevent subsequent opiate addiction after a short period of opioid treatment for temporary pain. Recent evidence indicates that selective inhibition of aldehyde dehydrogenase-2 (ALDH-2) reduces drug-seeking and trained self-administration of alcohol, cocaine and nicotine, apparently by preventing a concomitant surge of dopamine in the ventral tegmental area (VTA) and nucleus accumbens (NAc). Activation of the same dopaminergic pathway is also implicated in opioid-induced reinforcement. Therefore, we asked whether the selective ALDH-2 inhibitor, ANS-6637, would attenuate opioid self-administration in drug-naïve rats for opioid self-administration. Rats received oral doses of ANS-6637 (9, 18, 36 or 72 mg/kg) or an equal volume of control vehicle 2 h before exposure to remifentanil and a light cue to accentuate self-administration over 5 consecutive days. Self-administration and the numbers of lever presses on both active and inactive levers were recorded. ANS-6637 significantly reduces remifentanil self-administration over 5 sessions of treatment in rats without prior exposure to remifentanil. We also confirm that the highest dose of ANS-6637 (72 mg/kg) used in this study did not prevent remifentanil-induced analgesia using a classic hot plate test. Thus, ANS-6637 significantly reduces of initial exposure to remifentanil self-administration without affecting desired analgesia. These preliminary observations suggest that ANS-6637 appears to have potential value as a non-addictive therapeutic agent to prevent abuse of commonly used opiates in initiating pain management.
Authors
Rezvani, AH; Wells, C; Strumph, P; Diamond, I; Blackburn, BK; Levin, ED
MLA Citation
Rezvani, A. H., et al. “Risk for opioid abuse is diminished by inhibiting aldehyde dehydrogenase-2 (ALDH-2) in rats.” Journal of Drug and Alcohol Research, vol. 8, Jan. 2019. Scopus, doi:10.4303/jdar/236076.
URI
https://scholars.duke.edu/individual/pub1432954
Source
scopus
Published In
Journal of Drug and Alcohol Research
Volume
8
Published Date
DOI
10.4303/jdar/236076

JNJ-39220675, A NOVEL SELECTIVE HISTAMINE H-3 RECEPTOR ANTAGONIST, REDUCES THE ABUSE-RELATED EFFECTS OF ALCOHOL IN RATS

Authors
Galici, R; Rezvani, AH; Aluisio, L; Lord, B; Levin, ED; Fraser, I; Boggs, J; Welty, N; Shoblock, JR; Motley, ST; Letavic, MA; Carruthers, NI; Dugovic, C; Lovenberg, TW; Bonaventure, P
MLA Citation
Galici, R., et al. “JNJ-39220675, A NOVEL SELECTIVE HISTAMINE H-3 RECEPTOR ANTAGONIST, REDUCES THE ABUSE-RELATED EFFECTS OF ALCOHOL IN RATS.” Inflammation Research, vol. 60, SPRINGER BASEL AG, 2011, pp. S333–S333.
URI
https://scholars.duke.edu/individual/pub909559
Source
wos
Published In
Inflammation Research : Official Journal of the European Histamine Research Society ... [Et Al.]
Volume
60
Published Date
Start Page
S333
End Page
S333

Nicotinic receptor antagonists in rats

Nicotinic acetylcholine-receptor systems are critical neural components of cognitive functions. Nicotine and nicotinic agonists have been shown to improve cognition in rats in numerous studies [13-15, 27, 31, 59]. Similarly, nicotinic-receptor antagonists - the subject of this chapter - can cause cognitive impairments in rats. The use of nicotinic-receptor antagonists in an animal model of cognitive impairment has clinical relevance because it models the functional effect of nicotinic-receptor loss. Studies have shown that patients with Alzheimer’s disease suffer a dramatic reduction in hippocampal and cortical nicotine-receptor density that parallels the cognitive decline associated with this disease [56-58]. Significant nicotinic-receptor loss also occurs in Parkinson’s disease [9], and postmortem studies in schizophrenics show a decrease in the number of α7 nicotinic receptors in the brain [8, 19]. Both of these diseases can also include cognitive decline. Thus animal studies wherein nicotinic receptors are blocked with antagonists can be useful in developing animal models of how these diseases - Alzheimer’s, Parkinson’s, and schizophrenia - affect cognition.
Authors
Roegge, CS; Levin, ED
MLA Citation
Roegge, C. S., and E. D. Levin. “Nicotinic receptor antagonists in rats.” Animal Models of Cognitive Impairment, 2006, pp. 21–35.
URI
https://scholars.duke.edu/individual/pub1361627
Source
scopus
Published Date
Start Page
21
End Page
35

Oral 18-Methoxycoronaridine (18-MC) Decreases Nicotine Self-Administration in Rats

Tobacco addiction is a major problem worldwide with devastating health and socioeconomic consequences. Although several pharmacological treatments have been designed for combating this addiction, the development of more effective medications for the treatment of tobacco addiction remains a challenging goal. People use tobacco to obtain nicotine. Blocking the reinforcing effects of nicotine is key to combating tobacco addiction. Here, we briefly review the effects of administration of the iboga alkaloid derivative 18-methoxycoronaridine (18-MC) on nicotine intake. The systemic administration of 18-MC has been shown to decrease self-administration of several addictive drugs. Since oral administration of drugs is the preferred route for humans, the current study was conducted to determine the effect of oral 18-MC administration on intravenous nicotine self-administration in a rat model. Results showed that oral administration of 18-MC significantly reduced nicotine self-administration. It was also shown that 18-MC was significantly more effective in rats with lower nicotine self-administration rates than in those with higher nicotine intake. The finding that 18-MC is also effective in reducing nicotine self-administration when given orally makes it advantageous for further development as a possible novel therapy for combating smoking addiction.
Authors
Rezvani, AH; Glick, SD; Levin, ED
MLA Citation
Rezvani, A. H., et al. “Oral 18-Methoxycoronaridine (18-MC) Decreases Nicotine Self-Administration in Rats.” Neuroscience of Nicotine: Mechanisms and Treatment, 2019, pp. 493–97. Scopus, doi:10.1016/B978-0-12-813035-3.00059-9.
URI
https://scholars.duke.edu/individual/pub1435082
Source
scopus
Published Date
Start Page
493
End Page
497
DOI
10.1016/B978-0-12-813035-3.00059-9