Paternal Cannabis Exposure Prior to Mating, but Not Δ9-Tetrahydrocannabinol, Elicits Deficits in Dopaminergic Synaptic Activity in the Offspring.
Abstract
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.
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https://hdl.handle.net/10161/23942Published Version (Please cite this version)
10.1093/toxsci/kfab117Publication Info
Slotkin, Theodore A; Levin, Edward D; & Seidler, Frederic J (2021). Paternal Cannabis Exposure Prior to Mating, but Not Δ9-Tetrahydrocannabinol, Elicits
Deficits in Dopaminergic Synaptic Activity in the Offspring. Toxicological sciences : an official journal of the Society of Toxicology. 10.1093/toxsci/kfab117. Retrieved from https://hdl.handle.net/10161/23942.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Edward Daniel Levin
Professor in Psychiatry and Behavioral Sciences
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 cogn
Frederic J. Seidler
Assistant Research Professor Emeritus of Pharmacology & Cancer Biology
We study the effect of drugs, hormones and environmental factors on the intracellular
and extracellular biochemical signals that govern the development of mammalian neural
tissues, with particular emphasis on the biochemistry and molecular biology underlying
control of replication, differentiation, synaptogenesis and onset of synaptic function.
Ongoing projects comprise the following areas: (1) the role of endocrine and neurotrophic
factors in transmitter and receptor choice by developi
Theodore Alan Slotkin
Professor of Pharmacology and Cancer Biology
We study the interaction of drugs, hormones and environmental factors with the developing
organism, with particular emphasis on the fetal and neonatal nervous system. The
role of biochemical factors mediating development of nerve cells and other types of
tissue is a major thrust, since they influence the subsequent structural and physiological
status of critical organ systems. Ongoing projects comprise five areas: (1) Mechanisms
regulating development of synapses - role of endocrine and
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