ArticleBiological psychiatry2012
Proenkephalin mediates the enduring effects of adolescent cannabis exposure associated with adult opiate vulnerability.
Article in Biological psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
75 citing papers in PubMed, 131 citations in OpenAlex.
- Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans.Journal of addiction medicineTrial
- Epigenetic markers as predictors of neurotoxicity and abuse potential of psychotropic drugs: integration of epigenetic modifications in New Approach Methodologies.Archives of toxicology · 2026Review
- Concurrent maternal stress and THC exposure alters maternal regulation and downstream adolescent corticolimbic programs.Translational psychiatry · 2026Article
- Addictive drug abuse and depression-a focus on epigenetics.Communications biology · 2026Review
- Modifications on histone tails in psychiatric disorders.EC psychology and psychiatry · 2026Article
- Cannabinoid CB1 receptor and mu-opioid receptor interaction: new insights from conditional knockout mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- A Drd1-cre mouse line with nucleus accumbens gene dysregulation exhibits blunted fentanyl seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Corticostriatal cocaine-seeking ensembles are defined by differing gene expression from sucrose-seeking ensembles using a within-subject dual self-administration and seeking mouse model.Addiction neuroscience · 2025Article
- Divergent outcomes of delta 9 - tetrahydrocannabinol (THC) in adolescence on mesocortical dopamine and cognitive development in male and female mice.Psychopharmacology · 2025Article
- Neural basis of adolescent THC-induced potentiation of opioid responses later in life.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Neurological Disorders Induced by Drug Use: Effects of Adolescent and Embryonic Drug Exposure on Behavioral Neurodevelopment.International journal of molecular sciences · 2024Review
- Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia.bioRxiv : the preprint server for biology · 2024Article
- Review
- Association of cannabis use with depression among cancer patients.Preventive medicine reports · 2023Article
- Endocannabinoid signaling and epigenetics modifications in the neurobiology of stress-related disorders.Neuronal signaling · 2023Review
- Transcriptional and epigenetic regulation of microglia in substance use disorders.Molecular and cellular neurosciences · 2023Review
- Dose mediates the protracted effects of adolescent THC exposure on reward and stress reactivity in males relevant to perturbation of the basolateral amygdala transcriptome.Molecular psychiatry · 2023Article
- The Epigenetics of Migraine.International journal of molecular sciences · 2023Review
- Long-term effects of THC exposure on reward learning and motivated behavior in adolescent and adult male rats.Psychopharmacology · 2023Article
- An Individuality of Response to Cannabinoids: Challenges in Safety and Efficacy of Cannabis Products.Molecules (Basel, Switzerland) · 2023Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMarijuana use by teenagers often predates the use of harder drugs, but the neurobiological underpinnings of such vulnerability are unknown. Animal studies suggest enhanced heroin self-administration (SA) and dysregulation of the endogenous opioid system in the nucleus accumbens shell (NAcsh) of adults following adolescent Δ(9)-tetrahydrocannabinol (THC) exposure. However, a causal link between proenkephalin (Penk) expression and vulnerability to heroin has yet to be established.
methodsTo investigate the functional significance of NAcsh Penk tone, selective viral-mediated knockdown and overexpression of Penk was performed, followed by analysis of subsequent heroin SA behavior. To determine whether adolescent THC exposure was associated with chromatin alteration, we analyzed levels of histone H3 methylation in the NAcsh via chromatin immunoprecipitation at five sites flanking the Penk gene transcription start site.
resultsHere we show that regulation of the Penk opioid neuropeptide gene in NAcsh directly regulates heroin SA behavior. Selective viral-mediated knockdown of Penk in striatopallidal neurons attenuates heroin SA in adolescent THC-exposed rats, whereas Penk overexpression potentiates heroin SA in THC-naïve rats. Furthermore, we report that adolescent THC exposure mediates Penk upregulation through reduction of histone H3 lysine 9 (H3K9) methylation in the NAcsh, thereby disrupting the normal developmental pattern of H3K9 methylation.
conclusionsThese data establish a direct association between THC-induced NAcsh Penk upregulation and heroin SA and indicate that epigenetic dysregulation of Penk underlies the long-term effects of THC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.