Multi-, Inter-, and Transgenerational Effects of Drugs of Abuse on Behavior

Vassoler, Fair M.; Toorie, Anika M.; Byrnes, Elizabeth M.

doi:10.1007/7854_2019_106

Cited by 7 publications

(6 citation statements)

References 61 publications

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“…It is possible that this exposure influences the maturation of the dopamine system in females. In line with this idea, studies demonstrate that adolescent morphine exposure prior to pregnancy impacts the development of the opioid system in the next generation of females (Vassoler et al, 2019).…”

Section: Discussionmentioning

confidence: 80%

Prenatal opioid exposure inhibits microglial sculpting of the dopamine system selectively in adolescent male offspring

Smith

Lintz

Clark

et al. 2021

Preprint

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The current opioid epidemic has dramatically increased the number of children who are prenatally exposed to opioids, including oxycodone. However, little is know about the mechanisms by which prenatal opioid exposure leads to long term changes in reward circuit function and behavior. Microglia, the resident immune cells of the brain, are known to respond to perinatal opioid exposure and to sculpt neural circuits during development. Indeed, we recently found that microglial phagocytosis of dopamine D1 receptors in the nucleus accumbens (NAc) is required for the natural developmental decline in NAc-D1R that occurs between adolescence and adulthood. Morever, this microglial pruning occurs only in males, and is required for the normal developmental trajectory of social play behavior. Here, we show that maternal oxycodone self-administration during pregnancy leads to higher D1R density within the NAc in adult male, but not female, offspring in rats. Furthermore, adolescent microglial phagocytosis of D1R is reduced following prenatal oxycodone exposure. This work demonstrates for the first time that microglia play a key role in translating prenatal opioid exposure to long-term changes in neural systems.HighlightsPrenatal opioid exposure decreases offspring body weight in males and femalesPrenatal opioid exposure does not alter D2 receptor or Tyrosine Hydroxylase fiber density in either sexPrenatal opioid exposure increases nucleus accumbens dopamine D1 receptor expression in males but not femalesPrenatal opioid exposure decreases microglial phagocytosis of D1R in the nucleus accumbens in males only

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Section: Discussionmentioning

confidence: 80%

Prenatal opioid exposure inhibits microglial sculpting of the dopamine system selectively in adolescent male offspring

Smith

Lintz

Clark

et al. 2021

Preprint

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“…Epigenetic inheritance can result from modifications passed down from the mother, father, or both, resulting in either maternal, paternal, or parental epigenetic inheritance, respectively. Because these epigenetic modifications can be passed to the offspring, it is important to define the type of generational inheritance: multigenerational, intergenerational, or transgenerational [13].…”

Section: Generational Inheritancementioning

confidence: 99%

“…While the definition of transgenerational inheritance is fairly straightforward, defining interand multi-generational inheritance is slightly more difficult. Vassoler et al provide the simplest definitions for inter-and multi-generational inheritance [13]. If the F0 drug use occurs in males or in females prior to pregnancy, the germ cells, which will become the F1 generation, are exposed to the drug.…”

Section: Generational Inheritancementioning

confidence: 99%

Generational Effects of Opioid Exposure

2021

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The inheritance of substance abuse, including opioid abuse, may be influenced by genetic and non-genetic factors related to the environment, such as stress and socioeconomic status. These non-genetic influences on the heritability of a trait can be attributed to epigenetics. Epigenetic inheritance can result from modifications passed down from the mother, father, or both, resulting in either maternal, paternal, or parental epigenetic inheritance, respectively. These epigenetic modifications can be passed to the offspring to result in multigenerational, intergenerational, or transgenerational inheritance. Human and animal models of opioid exposure have shown generational effects that result in molecular, developmental, and behavioral alterations in future generations.

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“…In addition to recognizing that adolescent drug use may persistently influence susceptibility to drug abuse in adulthood, there is growing evidence for the transgenerational effects of drug-taking during adolescence [ 12 - 14 ]. These observations raise the hypothesis that epigenetic changes in one generation, following drug exposure in adolescence, promote the development of neurobiological changes in the next generation.…”

Section: Introductionmentioning

confidence: 99%

“…Such epigenetic changes include the addition of methyl or histone groups to DNA, and change the way genes are read and expressed [ 15 ]. As such, several studies have identified a range of transgenerational physiological and behavioral consequences following parental exposures to environmental toxins and drugs of abuse [ 12 , 14 , 16 , 17 ]. The direct effects of in-utero or adult pre-conception drug exposure on their offspring are not, however, the focus of this review, nor are the long-term effects of adolescent drug exposure on lifespan, which we have reviewed elsewhere [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Adolescent Substance Abuse, Transgenerational Consequences and Epigenetics

Salmanzadeh

Ahmadi-Soleimani

Azadi

et al. 2021

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: Adolescence is the transitional period between childhood and adulthood and a critical period in brain development. Adolescence in humans is also associated with increased expression of risk-taking behaviors. Epidemiological and clinical studies, for example, show a surge of drug abuse and raise the hypothesis that the adolescent brain undergoes critical changes resulting in diminished control. Determining how substance abuse during this critical period might cause long-term neurobiological changes in cognition and behavior is therefore critically important. The present work aims to provide an evaluation of the transgenerational and multi- generational phenotypes derived from parent animals exposed to drugs of abuse only during their adolescence. Specifically, we will consider changes found following administration of cannabinoids, nicotine, alcohol and opiates. In addition, epigenetic modifications of the genome following drug exposure will be discussed as emerging evidence of the underlying adverse transgenerational effects. Notwithstanding, much of the new data discussed here is from animal models, indicating that future clinical studies are much needed to better understand the neurobiological consequences and mechanisms of drug actions on the human brains’ development and maturation.

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Multi-, Inter-, and Transgenerational Effects of Drugs of Abuse on Behavior

Cited by 7 publications

References 61 publications

Prenatal opioid exposure inhibits microglial sculpting of the dopamine system selectively in adolescent male offspring

Prenatal opioid exposure inhibits microglial sculpting of the dopamine system selectively in adolescent male offspring

Generational Effects of Opioid Exposure

Adolescent Substance Abuse, Transgenerational Consequences and Epigenetics

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