About

Theodore Alan Slotkin is a Professor of Pharmacology and Cancer Biology at Duke University. He also holds positions as Professor in Neurobiology and in Psychiatry and Behavioral Sciences. His primary affiliation is with the Duke Department of Pharmacology and Cancer Biology, where he is involved in research and teaching activities. His work is associated with the Duke University School of Medicine, located at the B235 Lev Science Research Center in Durham, North Carolina. Further details about his research focus, background, and key contributions are not provided in the page text.

Research topics

• Medicine
• Biology
• Neuroscience
• Chemistry
• Physiology
• Psychology
• Environmental health
• Psychiatry
• Internal medicine
• Endocrinology
• Environmental chemistry

Selected publications

• Does consumption of a high-fructose diet during pregnancy and lactation exacerbate the effects of maternal exposure to cadmium on development and metabolic function of mouse offspring?

  Journal of Toxicology and Environmental Health · 2025-07-30 · 3 citations

  articleOpen access

  Exposures to pollutants rarely occur in isolation, often coexisting with other environmental stressors such as diet and may be particularly insidious in early life. The aim of this study was to examine effects of maternal exposure to cadmium (Cd) and consumption of a high-fructose diet (HFrD) on development of mouse offspring. Female CD-1 mice were administered either 0.5 or 5 ppm Cd in drinking water with or without an approximate 60% fructose diet for 3 weeks prior to mating. Dams were maintained on the same treatment until postnatal day (PND) 16. Cadmium concentrations in maternal, fetal, and neonatal liver increased in a concentration-dependent manner irrespective of diet. Endpoints known to be associated with Cd or HFrD adverse effects were assessed longitudinally in offspring from birth to young adulthood, including growth trajectory, pubertal development, body composition, glycemic tolerance and hepatic lipid accumulation. Maternal exposure to either Cd or HFrD alone significantly advanced onset of puberty, hypoglycemia, and reduced adiposity in adulthood. HFrD rarely exacerbated metal-initiated effects in most of the endpoints examined outside of pubertal timing. Because of chronic effects attributed to Cd or HFrD on metabolic function (e.g. glucose tolerance), transcriptomics and gene methylation analyses were performed on livers from neonatal and adult offspring. Data were largely consistent with phenotypic findings. In summary, maternal exposure to Cd or HFrD alone perturbed growth and development, producing long-lasting changes in metabolic function in adult offspring. HFrD did not appear to significantly exaggerate adverse outcomes attributed to metal exposure in the endpoints examined.

  PublisherOA PDFDOI

• Cyclic Mechanism Affects Lumbar Spine Creep Response

  Annals of Biomedical Engineering · 2024-08-04

  article
  PublisherDOI

• Temporally non-regular patterns of deep brain stimulation (DBS) enhance assessment of evoked potentials while maintaining motor symptom management in Parkinson's disease (PD)

  Brain stimulation · 2023-10-19 · 12 citations

  articleOpen access

  BACKGROUND: Traditional deep brain stimulation (DBS) at fixed regular frequencies (>100 Hz) is effective in treating motor symptoms of Parkinson's disease (PD). Temporally non-regular patterns of DBS are a new parameter space that may help increase efficacy and efficiency. OBJECTIVE: To compare the effects of temporally non-regular patterns of DBS to traditional regularly-spaced pulses. METHODS: We simultaneously recorded local field potentials (LFP) and monitored motor symptoms (tremor and bradykinesia) in persons with PD during DBS in subthalamic nucleus (STN). We quantified both oscillatory activity and DBS local evoked potentials (DLEPs) from the LFP. RESULTS: Temporally non-regular patterns were as effective as traditional pulse patterns in modulating motor symptoms, oscillatory activity, and DLEPs. Moreover, one of our novel patterns enabled recording of longer duration DLEPs during clinically effective stimulation. CONCLUSIONS: Stimulation gaps of 50 ms can be used to increase efficiency and to enable regular assessment of long-duration DLEPs while maintaining effective symptom management. This may be a promising paradigm for closed-loop DBS with biomarker assessment during the gaps.

  PublisherOA PDFDOI

• Mohamed Bahie Abou-Donia: Pioneer in organophosphorus-induced neurotoxicity

  NeuroToxicology · 2023-12-05

  article1st authorCorresponding
  PublisherDOI

• Developmental exposure to the flame retardant, triphenyl phosphate, causes long‐lasting neurobehavioral and neurochemical dysfunction

  Birth Defects Research · 2022-11-11 · 11 citations

  articleOpen access

  BACKGROUND: Human exposures to organophosphate flame retardants result from their use as additives in numerous consumer products. These agents are replacements for brominated flame retardants but have not yet faced similar scrutiny for developmental neurotoxicity. We examined a representative organophosphate flame retardant, triphenyl phosphate (TPP) and its potential effects on behavioral development and dopaminergic function. METHODS: ) via subcutaneous osmotic minipumps, begun preconception and continued into the early postnatal period. Offspring were administered a battery of behavioral tests from adolescence into adulthood, and littermates were used to evaluate dopaminergic synaptic function. RESULTS: Offspring with TPP exposures showed increased latency to begin eating in the novelty-suppressed feeding test, impaired object recognition memory, impaired choice accuracy in the visual signal detection test, and sex-selective effects on locomotor activity in adolescence (males) but not adulthood. Male, but not female, offspring showed marked increases in dopamine utilization in the striatum, evidenced by an increase in the ratio of the primary dopamine metabolite (3,4-dihydroxyphenylacetic acid) relative to dopamine levels. CONCLUSIONS: These results indicate that TPP has adverse effects that are similar in some respects to those of organophosphate pesticides, which were restricted because of their developmental neurotoxicity.

  PublisherOA PDFDOI

• Persistent neurobehavioral and neurochemical anomalies in middle-aged rats after maternal diazinon exposure

  Toxicology · 2022-04-01 · 10 citations

  articleOpen access
  PublisherOA PDFDOI

• Paternal Cannabis Exposure Prior to Mating, but Not Δ9-Tetrahydrocannabinol, Elicits Deficits in Dopaminergic Synaptic Activity in the Offspring

  Toxicological Sciences · 2021-09-24 · 11 citations

  articleOpen access1st authorCorresponding

  The legalization and increasing availability of cannabis products raises concerns about the impact on offspring of users, and little has appeared on the potential contribution of paternal use. We administered cannabis extract to male rats prior to mating, with two different 28-day exposures, one where there was a 56-day interval between the end of exposure and mating ("Early Cannabis"), and one just prior to mating ("Late Cannabis"); the extract delivered 4 mg/kg/day of the main psychoactive component, Δ9-tetrahydrocannabinol. We then assessed the impact on dopamine (DA) systems in the offspring from the onset of adolescence (postnatal day 30) through middle age (postnatal day 150), measuring the levels of DA and its primary metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) in various brain regions. Paternal cannabis with either regimen elicited a profound and persistent deficit in DA utilization (DOPAC/DA ratio) in the offspring, indicative of subnormal presynaptic activity. However, the two regimens differed in the underlying mechanism, with Early Cannabis reducing DOPAC whereas Late Cannabis increased DA and elicited a smaller reduction in DOPAC. Effects were restricted to male offspring. The effects of cannabis were not reproduced by equivalent exposure to its Δ9-tetrahydrocannabinol, nor did we see the effects with perinatal exposure to tobacco smoke or some of its fetotoxic contributors (benzo[a]pyrene without or with nicotine). Our studies provide some of the first evidence for adverse effects of paternal cannabis administration on neurodevelopment in the offspring, and reinforce the important consequences of paternal drug use in the preconception period.

  PublisherOA PDFDOI

• Neurobehavioral anomalies in zebrafish after sequential exposures to DDT and chlorpyrifos in adulthood: Do multiple exposures interact?

  Neurotoxicology and Teratology · 2021-04-24 · 13 citations

  articleOpen access
  PublisherOA PDFDOI

• Analysis of polycyclic aromatic hydrocarbon intake in the US adult population from NHANES 2005–2014 identifies vulnerable subpopulations, suggests interaction between tobacco smoke exposure and sociodemographic factors

  Environmental Research · 2021 · 15 citations

  • Environmental health
  • Medicine
  • Environmental chemistry
  PublisherOA PDFDOI

• The sea urchin embryo, an invertebrate model for mammalian developmental neurotoxicity, reveals multiple neurotransmitter mechanisms for effects of chlorpyrifos: Therapeutic interventions and a comparison with the monoamine depleter, reserpine

  UNC Libraries · 2020-10-31

  articleOpen access

  Lower organisms show promise for the screening of neurotoxicants that might target mammalian brain development. Sea urchins use neurotransmitters as embryonic growth regulatory signals, so that adverse effects on neural substrates for mammalian brain development can be studied in this simple organism. We compared the effects of the organophosphate insecticide, chlorpyrifos in sea urchin embryos with those of the monoamine depleter, reserpine, so as to investigate multiple neurotransmitter mechanisms involved in developmental toxicity and to evaluate different therapeutic interventions corresponding to each neurotransmitter system. Whereas reserpine interfered with all stages of embryonic development, the effects of chlorpyrifos did not emerge until the mid-blastula stage. After that point, the effects of the two agents were similar. Treatment with membrane permeable analogs of the monoamine neurotransmitters, serotonin and dopamine, prevented the adverse effects of either chlorpyrifos or reserpine, despite the fact that chlorpyrifos works simultaneously through actions on acetylcholine, monoamines and other neurotransmitter pathways. This suggests that different neurotransmitters, converging on the same downstream signaling events, could work together or in parallel to offset the developmental disruption caused by exposure to disparate agents. We tested this hypothesis by evaluating membrane permeable analogs of acetylcholine and cannabinoids, both of which proved effective against chlorpyrifos- or reserpine-induced teratogenesis. Invertebrate test systems can provide both a screening procedure for mammalian neuroteratogenesis and may uncover novel mechanisms underlying developmental vulnerability as well as possible therapeutic approaches to prevent teratogenesis.

  PublisherDOI

Recent grants

• NIH Grant R01DA014247

  NIH · $693k · 2005

• NIH Grant P30MH040159

  NIH · $6.9M · 2000

• NIH Grant R01HD009713

  NIH · $3.3M · 2005

• NIH Grant R01ES010387

  NIH · $963k · 2006

Frequent coauthors

• Frederic J. Seidler

  Duke University

  958 shared

• William L. Whitmore

  233 shared

• Edward D. Levin

  Duke Medical Center

  191 shared

• Jorge Bartolomé

  Duke Medical Center

  162 shared

• Christopher Lau

  Duke Medical Center

  152 shared

• E.C. McCook

  81 shared

• Joseph Yanai

  Duke Medical Center

  68 shared

• Maria B. Bartolome

  66 shared

Labs

• Research by LabPI