Paternal THC exposure in rats causes long-lasting neurobehavioral effects in the offspring.
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2019-07
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Abstract
Developmental neurotoxicity of a wide variety of toxicants mediated via maternal exposure during gestation is very well established. In contrast, the impacts of paternal toxicant exposure on offspring neurobehavioral function are much less well studied. A vector for paternal toxicant exposure on development of his offspring has been identified. Sperm DNA can be imprinted by chemical exposures of the father. Most but not all of the epigenetic marks in sperm are reprogrammed after fertilization. The persisting epigenetic marks can lead to abnormal genetic expression in the offspring. We have found that paternal delta-9-tetrohydrocannabinol (THC) exposure in rats causes changes in methylation of sperm (Murphy et al., 2018). This is similar to cannabis-associated changes in sperm DNA methylation we found in human males who smoke cannabis (Murphy et al., 2018). In the current study we investigated the intergeneration effects of THC exposure of young adult male rats (0 or 2 mg/kg/day orally for 12 days) to the neurobehavioral development of their offspring. This paternal THC exposure was not found to significantly impact the clinical health of the offspring, including litter size, sex ratio, pup birth weight, survival and growth. However, it did cause a long-lasting significant impairment in attentional performance in the offspring relative to controls when they were tested in adulthood. There was also a significant increase in habituation of locomotor activity in the adult offspring of the males exposed to THC prior to mating. This study shows that premating paternal THC exposure even at a modest dose for a brief period can cause deleterious long-term behavioral effects in the offspring, notably significant impairment in an operant attention task. Further research should be conducted to determine the degree to which this type of risk is seen in humans and to investigate the mechanisms underlying these effects and possible treatments to ameliorate these long-term adverse behavioral consequences of paternal THC exposure.
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Levin, Edward D, Andrew B Hawkey, Brandon J Hall, Marty Cauley, Susan Slade, Elisa Yazdani, Bruny Kenou, Hannah White, et al. (2019). Paternal THC exposure in rats causes long-lasting neurobehavioral effects in the offspring. Neurotoxicology and teratology, 74. p. 106806. 10.1016/j.ntt.2019.04.003 Retrieved from https://hdl.handle.net/10161/29511.
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Scholars@Duke
Amir H. Rezvani
My research and teaching interests have been primarily focused on the following areas:
Alcoholism: I work with "alcoholic" rats with genetic predisposition!" We use selectively-bred alcohol preferring rats as an animal model of human alcoholism for developing better pharmacological treatments for alcoholism. Recently, we are working on several novel promising "anti-craving" compounds for the treatment of alcoholism. We are also studying the interaction between alcohol drinking and nicotine intake.
Nicotine Addiction: We have been studying age and sex differences in i.v. nicotine self-administration in rats. We have found that pattern of drug intake is both age- and sex-dependent. Our lab is also exploring different neuronal targets for developing better pharmacologic treatment for nicotine addiction.
Sustained Attention: Another aspect of our research is studying the role of the neuronal nicotinic and other neuronal systems in sustained attention using a rodent model. We have shown, nicotine (not smoking!) and nicotinic compounds improve attention in rats. A majority of people with schizophrenia smoke and they smoke heavily. Thus, it is important to understand the interaction of antipsychotic medications and nicotine in sustained attention. This has been another aspect of our research with interesting results. Presently, we are testing novel nicotinic compounds for improving pharmacologically-impaired sustained attention.
Teaching: I love to teach and interact with students. Since arriving at Duke in 1999, I have been team-teaching the popular alcohol course (Psych 206-01R; Alcohol: Brain, Society and Individual). I also enjoy mentoring undergrad students who are interested in science and enjoy working in the lab with cute little creatures!.
Community: I am a member of the Board of Directors of Triangle Residential Options for Substance Abusers (TROSA), a self-supported therapeutic community in Durham. I also give seminars and workshops on addiction around the country.
Susan Kay Murphy
Dr. Murphy is a tenured Associate Professor in the Department of Obstetrics and Gynecology and serves as Chief of the Division of Reproductive Sciences. As a molecular biologist with training in human epigenetics, her research interests are largely centered around the role of epigenetic modifications in health and disease.
Dr. Murphy has ongoing projects on gynecologic malignancies, including approaches to eradicate ovarian cancer cells that survive chemotherapy and later give rise to recurrent disease. Dr. Murphy is actively involved in many collaborative projects relating to the Developmental Origins of Health and Disease (DOHaD).
Her lab is currently working on preconception environmental exposures in males, particularly on the impact of cannabis on the sperm epigenome and the potential heritability of these effects. They are also studying the epigenetic and health effects of in utero exposures, with primary focus on children from the Newborn Epigenetics STudy (NEST), a pregnancy cohort she co-founded who were recruited from central North Carolina between 2005 and 2011. Dr. Murphy and her colleagues continue to follow NEST children to determine relationships between prenatal exposures and later health outcomes.
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