Nature neuroscience, 2013-01, Vol.16 (1), p.42-47
2013
Details
- Autor(en) / Beteiligte
- Titel
- Epigenetic inheritance of a cocaine-resistance phenotype
- Ist Teil von
- Nature neuroscience, 2013-01, Vol.16 (1), p.42-47
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- Psychology & Behavioral Sciences Collection (EBSCO)
- Beschreibungen/Notizen
- We delineated a heritable phenotype resulting from the self-administration of cocaine in rats. We observed delayed acquisition and reduced maintenance of cocaine self-administration in male, but not female, offspring of sires that self-administered cocaine. Brain-derived neurotrophic factor (Bdnf) mRNA and BDNF protein were increased in the medial prefrontal cortex (mPFC), and there was an increased association of acetylated histone H3 with Bdnf promoters in only the male offspring of cocaine-experienced sires. Administration of a BDNF receptor antagonist (the TrkB receptor antagonist ANA-12) reversed the diminished cocaine self-administration in male cocaine-sired rats. In addition, the association of acetylated histone H3 with Bdnf promoters was increased in the sperm of sires that self-administered cocaine. Collectively, these findings indicate that voluntary paternal ingestion of cocaine results in epigenetic reprogramming of the germline, having profound effects on mPFC gene expression and resistance to cocaine reinforcement in male offspring.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-6256eISSN: 1546-1726DOI: 10.1038/nn.3280Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3531046
- Format
- –
- Schlagworte
- Acetylation - drug effects, Animals, Animals, Newborn, Azepines - pharmacology, Benzamides - pharmacology, Brain-derived neurotrophic factor, Brain-Derived Neurotrophic Factor - genetics, Brain-Derived Neurotrophic Factor - metabolism, Chromatin Immunoprecipitation, Cocaine, Cocaine - administration & dosage, Cocaine-Related Disorders - genetics, Conditioning, Operant - drug effects, Conditioning, Operant - physiology, Disease Models, Animal, DNA methylation, Dopamine Uptake Inhibitors - administration & dosage, Dose-Response Relationship, Drug, Drug dosages, Epigenetic inheritance, Epigenetics, Epigenomics, Feeding Behavior - drug effects, Female, Females, Food Preferences - drug effects, Food Preferences - physiology, Gene expression, Genetic aspects, Genotype & phenotype, Grooming - drug effects, Histones - metabolism, Influence, Male, Males, Morphine, Neurosciences, Phenotype, Prefrontal Cortex - drug effects, Prefrontal Cortex - metabolism, Rats, Rats, Sprague-Dawley, Receptor, trkB - antagonists & inhibitors, Reinforcement (Psychology), RNA, Messenger - metabolism, RNA, Messenger - pharmacology, Self Administration, Sex Characteristics, Sucrose - administration & dosage, Sweetening Agents - administration & dosage