Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour

Le, Qiumin; Yan, Biao; Yu, Xiangchen; Li, Yanqing; Song, Haikun; Zhu, Huiwen; Hou, Weiqing; Ma, Dingailu; Wu, Feizhen; Zhou, Yuqing; Ma, Lan

doi:10.1038/ncomms15527

Cited by 74 publications

(87 citation statements)

References 52 publications

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“…This report adds to a growing body of evidence that paternal cocaine exposure produces altered cocaine reward processing and cocaine addiction‐related behavior in first‐generation offspring. Two recent publications indicate that the male offspring of sires exposed to an extensive cocaine self‐administration regimen have altered cocaine self‐administration (Le et al., ; Vassoler et al., ). The current results are consistent with these studies, showing that male, but not female offspring of cocaine‐taking sires have blunted cocaine sensitization.…”

Section: Discussionmentioning

confidence: 99%

“…Several reports have consistently shown that sire exposure to cocaine influences cocaine‐associated behaviors in the next generation. For example, the progeny of sires that self‐administered or received non‐contingent cocaine displayed reduced cocaine self‐administration in male offspring (Le et al., ; Vassoler et al., ). Blunted cocaine‐conditioned reward in female offspring of sires that received non‐contingent cocaine also has been observed (Fischer, Rice, Martinez Rivera, Donohoe, & Rajadhyaksha, ).…”

Section: Introductionmentioning

confidence: 99%

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Impaired cocaine‐induced behavioral plasticity in the male offspring of cocaine‐experienced sires

Wimmer

Vassoler

White

et al. 2019

Eur J of Neuroscience

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Our previous work indicated that male, but not female, offspring of cocaine‐experienced sires display blunted cocaine self‐administration. We extended this line of investigation to examine behavioral sensitization, a commonly used model of cocaine‐induced behavioral and neuronal plasticity. Results indicated that male, but not female, offspring of cocaine‐taking sires showed deficits in the ability of repeated systemic cocaine injections to induce augmented locomotor activity. The reduced cocaine sensitization phenotype in male progeny was associated with changes in histone post‐translational modifications, epigenetic processes that regulate gene expression by controlling the accessibility of genes to transcriptional machinery, in the nucleus accumbens of first‐generation male progeny. Thus, five histone post‐translational modifications were significantly altered in the male progeny of cocaine‐exposed sires. In contrast, self‐administration of nicotine was unaltered in male and female offspring suggesting that the intergenerational effects of paternal cocaine taking may be drug‐specific. Interestingly, the reduced sensitivity to cocaine previously observed in the male offspring of cocaine‐taking sires dissipated in the grand‐offspring. Both male and female grand‐progeny of cocaine‐exposed sires showed unaltered cocaine‐induced behavioral sensitization and cocaine self‐administration. Taken together, these findings indicate that paternal cocaine taking produces changes in multiple cocaine addiction‐related behaviors in male progeny, which do not persist beyond the first generation of offspring. Moreover, the altered sensitivity to cocaine in first‐generation male progeny of cocaine‐sired male offspring was associated with epigenetic modifications in the nucleus accumbens, a nucleus that plays a critical role in cocaine‐associated behavioral plasticity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impaired cocaine‐induced behavioral plasticity in the male offspring of cocaine‐experienced sires

Wimmer

Vassoler

White

et al. 2019

Eur J of Neuroscience

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“…Following separation into “Addict” F0 and “Non‐addict” F0 rats, they were bred with naïve females to generate F1 and F2 offspring. The “Addict” F1 and F2 offspring displayed increased cocaine self‐administration, while no effect on cocaine self‐administration was detected in the “Non‐addict” F1 and F2 offspring (Le et al ., ). Previous studies that have separated mouse drug‐response into high and low responders have identified numerous genetic differences between these sub‐populations (Radcliffe et al ., ; He et al ., ; Belknap et al ., ).…”

Section: Cocainementioning

confidence: 97%

“…In a study by Le et al . (), Sprague Dawley rats were trained to self‐administer cocaine and then separated into “Addict” F0 rats (top 25% of responders) and “Non‐addict” F0 rats (bottom 40% of responders). Following separation into “Addict” F0 and “Non‐addict” F0 rats, they were bred with naïve females to generate F1 and F2 offspring.…”

Section: Cocainementioning

confidence: 99%

“…Specifically, cocaine‐sired Sprague Dawley offspring display increased medial prefrontal cortex (mPFC) BDNF mRNA and protein levels (Vassoler et al ., ). Additionally, elevation of BDNF level in cocaine‐sired offspring was shown to correlate with cocaine intake of the F0 Sprague Dawley male (Le et al ., ). Also, an increased association of acetylated histone H3 with Bdnf promoters was observed in the mPFC of cocaine‐sired Sprague Dawley rats, which suggests a potential epigenetic mechanism that may mediate the multigenerational phenotype (Vassoler et al ., ).…”

Section: Cocainementioning

confidence: 99%

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Multigenerational and transgenerational effects of paternal exposure to drugs of abuse on behavioral and neural function

Goldberg

Gould

2018

Eur J of Neuroscience

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Addictions are highly heritable disorders, with heritability estimates ranging from 39% to 72%. Multiple studies suggest a link between paternal drug abuse and addiction in their children. However, patterns of inheritance cannot be explained purely by Mendelian genetic mechanisms. Exposure to drugs of abuse results in epigenetic changes that may be passed on through the germline. This mechanism of epigenetic transgenerational inheritance may provide a link between paternal drug exposure and addiction susceptibility in the offspring. Recent studies have begun to investigate the effect of paternal drug exposure on behavioral and neurobiological phenotypes in offspring of drug-exposed fathers in rodent models. This review aims to discuss behavioral and neural effects of paternal exposure to alcohol, cocaine, opioids, and nicotine. Although a special focus will be on addiction-relevant behaviors, additional behavioral effects including cognition, anxiety, and depressive-like behaviors will be discussed.

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Paternal exposure to recreational drugs before conception and its effect on live‐born offspring: A scoping review

Verstegen

Guo

Langenberg-Ververgaert

et al. 2020

Birth Defects Research

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BackgroundMen of reproductive age increasingly use recreational drugs. While many of these substances may reduce the quantity and quality of sperm, less is known about the effects of these exposures on their offspring. We performed a scoping review to summarize the available literature and identify areas for future research on the outcome of live‐born offspring of fathers who were exposed to recreational drugs before conception.MethodsA systematic search was conducted of the Medline, EMBASE, and Web of Science databases, which included keywords for the following substances: cannabis‐related products, cocaine, heroin, hallucinogens, ecstasy and amphetamines. In total, 2,983 records were screened, and 129 publications were selected for full‐text assessment. Publications were included if (a) the timing of exposure included the preconceptional period, and (b) if outcomes in live‐born offspring were compared with an unexposed group.ResultsWe included 30 publications, of which 15 animal studies and 15 human studies. Animal studies showed neurocognitive abnormalities, in particular in male offspring. Interestingly, these outcomes depend significantly on the method of exposure (i.e., fixed‐dose administration vs. variable self‐administration, which mimics addiction). Human studies were limited to specific congenital malformations and childhood cancers, which showed small increased odds ratios.ConclusionsWhile animal studies describe impaired neurocognitive outcomes following paternal exposure to recreational drugs, data in humans is currently lacking. Human studies require sound methodology in order to confirm findings on congenital malformations and childhood cancers. In addition, future neurocognitive studies require parental neurocognitive assessments to correct for confounding effects (i.e., role of genetics).

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Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour

Cited by 74 publications

References 52 publications

Impaired cocaine‐induced behavioral plasticity in the male offspring of cocaine‐experienced sires

Impaired cocaine‐induced behavioral plasticity in the male offspring of cocaine‐experienced sires

Multigenerational and transgenerational effects of paternal exposure to drugs of abuse on behavioral and neural function

Paternal exposure to recreational drugs before conception and its effect on live‐born offspring: A scoping review

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