ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
A Functional 3'UTR Polymorphism (rs2235749) of Prodynorphin Alters microRNA-365 Binding in Ventral Striatonigral Neurons to Influence Novelty Seeking and Positive Reward Traits.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Role of microRNAs in the pathophysiology of addiction.Wiley interdisciplinary reviews. RNA · 2021Pooled it
- Trace amine-associated receptor gene polymorphism increases drug craving in individuals with methamphetamine dependence.PloS one · 2019Trial
- Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3'-UTR of theInternational journal of molecular sciences · 2022Article
- Sex- and genotype-dependent nicotine plus cue-primed reinstatement is enhanced in adolescent Sprague Dawley rats containing the humanFrontiers in psychiatry · 2022Article
- Epigenetic and Transcriptional Control of the Opioid Prodynorphine Gene: In-Depth Analysis in the Human Brain.Molecules (Basel, Switzerland) · 2021Review
- Molecular windows into the human brain for psychiatric disorders.Molecular psychiatry · 2019Review
- Sex differences in neural mechanisms mediating reward and addiction.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Review
- Regulation of chromatin and gene expression by metabolic enzymes and metabolites.Nature reviews. Molecular cell biology · 2018Review
- Evaluation of prodynorphin gene polymorphisms and their association with heroin addiction in a sample of the southeast Iranian population.Molecular biology research communications · 2018Article
- Shaping vulnerability to addiction - the contribution of behavior, neural circuits and molecular mechanisms.Neuroscience and biobehavioral reviews · 2018Review
- Gender-specific association of functionalNeuropsychiatric disease and treatment · 2018Article
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11 authors at 1 institution in 1 country.
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Abstract
Genetic factors impact behavioral traits relevant to numerous psychiatric disorders and risk-taking behaviors, and different lines of evidence have indicated that discrete neurobiological systems contribute to such individual differences. In this study, we explored the relationship of genetic variants of the prodynorphin (PDYN) gene, which is enriched in the striatonigral/striatomesencephalic pathway, a key neuronal circuit implicated in positive 'Go' behavioral choice and action. Our multidisciplinary approach revealed that the single nucleotide polymorphism (SNP) rs2235749 (in high linkage disequilibrium with rs910080) modifies striatal PDYN expression via impaired binding of miR-365, a microRNA that targets the PDYN 3'-untranslated region (3'UTR), and is significantly associated to novelty- and reward-related behavioral traits in humans and translational animal models. Carriers of the rs2235749G allele exhibited increased levels of PDYN 3'UTR in vitro and had elevated mRNA expression in the medial nucleus accumbens shell (NAcSh) and caudate nucleus in postmortem human brains. There was an association of rs2235749 with novelty-seeking trait and a strong genotype-dose association with positive reinforcement behavior in control subjects, which differed in cannabis-dependent individuals. Using lentiviral miRZip-365 constructs selectively expressed in Pdyn-neurons of the NAcSh, we demonstrated that the Pdyn-miR365 interaction in the NAcSh directly influences novelty-seeking exploratory behavior and facilitates self-administration of natural reward. Overall, this translational study suggests that genetically determined miR-365-mediated epigenetic regulation of PDYN expression in mesolimbic striatonigral/striatomesencephalic circuits possibly contributes to novelty seeking and positive reinforcement traits.
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