Maternally Transmitted Opiate Abuse Vulnerability
Principal Investigator: Elizabeth Byrnes
Affiliation: Tufts University
Abstract: Many studies have demonstrated that the hereditary nature of drug abuse is due to both genetic and environmental factors. Recent findings demonstrate that one mechanism regulating interactions between genes and the environment are epigenetic modifications. The term epigenetics refers to DNA and histone protein modifications that regulate gene expression and which are transmitted from a mother cell to a daughter cell or from a parent to a progeny, but which do not change the underlying DNA sequence. While it is clear that epigenetic modifications can be passed from one generation to the next, the mechanisms involved in the transmission of these effects are not fully understood. Several recent findings indicate that the maternal environment, both pre- and postnatal, may play a critical role in epigenetic transfer. To date, the role of epigenetics in familial patterns of drug abuse has not been well studied. Prescription narcotics use by adolescent females has increased dramatically in the past decade. We have developed an animal model of adolescent morphine exposure in female rats to examine the long-term consequences of opiate use during this unique developmental period. Our findings demonstrate that in addition to significant alterations in gene expression in adult female rats exposed to morphine during adolescence, the offspring of adolescent-exposed females demonstrate enhanced responsiveness to morphine. These offspring effects suggest adolescent morphine exposure increases the risk of drug abuse in the next generation. One of important aspect of this model is that adolescent morphine-exposed females are drug-free for at least 10 days prior to mating. Thus, developing offspring are never directly exposed to morphine. This means that any effect observed in the offspring is maternally-derived. The purpose of the present proposal is to determine the role of epigenetics in the long-term effects of adolescent morphine exposure on both the female and her offspring. The current proposal will identify transgenerational epigenetic modifications in the adult offspring of females exposed to morphine during adolescent development (Specific Aim 1). It will also examine possible changes in the maternal environment which may play a role in the transmission of these offspring effects (Specific Aim 2). Finally, we will test whether postnatal manipulations can ameliorate or prevent the transgenerational effects of adolescent morphine exposure (Specific Aim 3). Understanding how drug-induced alterations in morphine sensitivity may be passed from one generation to the next will help identify basic mechanisms underlying familial patterns of drug abuse as well as possible interventions. PUBLIC HEALTH RELEVANCE: The goal of this project is to understand how mothers who are exposed to narcotics during adolescence increase the probability of drug abuse in their future offspring. These studies will provide a foundation for understanding the role of maternal factors in familial patterns of drug abuse.
Funding Period: -------------------- - -------------------2
more information: NIH RePORT
- Adolescent opiate exposure in the female rat induces subtle alterations in maternal care and transgenerational effects on play behaviorNicole L Johnson
Department of Biomedical Science, Cummings School of Veterinary Medicine, Tufts University North Grafton, MA, USA
Front Psychiatry 2:29. 2011..Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring...
- Cannabinoid exposure in adolescent female rats induces transgenerational effects on morphine conditioned place preference in male offspringJohn J Byrnes
Department of Biomedical Sciences, Tufts University, Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA
J Psychopharmacol 26:1348-54. 2012..Both adolescent and adult WIN-F1offspring exhibited greater sensitivity to morphine CPP than their VEH-F1 counterparts. Collectively, the findings provide additional evidence of transgenerational effects of adolescent drug use...
- Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor functionJohn J Byrnes
Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA
Psychopharmacology (Berl) 227:263-72. 2013..Given the significant role that opioids play in neuroendocrine function, exposure to opiates during this critical developmental period could have significant consequences for the female, as well as her offspring...
- Environmental enrichment effects on the neurobehavioral profile of selective outbred trait anxiety ratsRebecca Ravenelle
Department of Psychology, University of Massachusetts Boston, Boston, MA 02125, USA
Behav Brain Res 252:49-57. 2013..The results suggest that selectively-bred trait anxiety rats show state anxiety that is influenced by rearing environments, and D2 protein levels and BDNF/TrkB signaling may differentially contribute to integrating these effects. ..
- The impact of exposure to addictive drugs on future generations: Physiological and behavioral effectsF M Vassoler
Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, Grafton, MA 01536, USA Electronic address
Neuropharmacology 76:269-75. 2014..The potential epigenetic mechanisms underlying the transmission of these phenotypes across generations also are detailed. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'...
- Female adolescent exposure to cannabinoids causes transgenerational effects on morphine sensitization in female offspring in the absence of in utero exposureFair M Vassoler
Department of Biomedical Sciences, Tufts University, Grafton, USA
J Psychopharmacol 27:1015-22. 2013..Together, these findings demonstrate transgenerational effects of adolescent exposure to cannabinoids in the absence of any in utero exposure. ..
- Next generation effects of female adolescent morphine exposure: sex-specific alterations in response to acute morphine emerge before pubertyFair M Vassoler
Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, North Grafton, Massachusetts, USA
Behav Pharmacol 25:173-81. 2014....
- Adolescent opioid exposure in female rats: transgenerational effects on morphine analgesia and anxiety-like behavior in adult offspringJohn J Byrnes
Department of Biomedical Sciences, Section of Reproduction and Neuroscience, Tufts University, Cummings School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536, United States
Behav Brain Res 218:200-5. 2011..The findings indicate that prior opiate exposure during early adolescence in females produces sex-specific alterations of both emotionality and morphine sensitivity in their progeny...