{"doi":"10.1101/2023.01.03.522600","title":"Paternal morphine exposure enhances morphine self-administration and induces region-specific neural adaptations in reward-related brain regions of male offspring","abstract":"Background: A growing body of preclinical studies report that preconceptional experiences can have a profound and long-lasting impact on adult offspring behavior and physiology. However, less is known about paternal drug exposure and its effects on reward sensitivity in the next generation. Methods: Adult male rats self-administered morphine for 65 days; controls received saline. Sires were bred to drug-naïve dams to produce first-generation (F1) offspring. Morphine, cocaine, and nicotine self-administration were measured in adult F1 progeny. Molecular correlates of addiction-like behaviors were measured in reward-related brain regions of drug naïve F1 offspring. Results: Male, but not female offspring produced by morphine-exposed sires exhibited dose-dependent increased morphine self-administration and increased motivation to earn morphine infusions under a progressive ratio schedule of reinforcement. This phenotype was drug-specific as self-administration of cocaine, nicotine, and sucrose were not altered by paternal morphine history. The male offspring of morphine-exposed sires also had increased expression of mu-opioid receptors in the ventral tegmental area but not in the nucleus accumbens. Conclusions: Paternal morphine exposure increased morphine addiction-like behavioral vulnerability in male but not female progeny. This phenotype is likely driven by long-lasting neural adaptations within the reward neural brain pathways.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392844,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":530447,"name":"Alexandra S. Ellis","orcid":"0000-0002-8093-7500","position":1,"is_corresponding":false},{"id":531157,"name":"Angela R. Bongiovanni","orcid":null,"position":2,"is_corresponding":false},{"id":649910,"name":"Drew R. Peterson","orcid":"0000-0001-7882-629X","position":3,"is_corresponding":false},{"id":440208,"name":"Charlotte C. Bavley","orcid":"0000-0001-7273-7392","position":4,"is_corresponding":false},{"id":649911,"name":"Reza Karbalaei","orcid":"0000-0002-2982-5466","position":5,"is_corresponding":false},{"id":891095,"name":"Hannah L. Mayberry","orcid":null,"position":6,"is_corresponding":false},{"id":1166816,"name":"Shivam Bhakta","orcid":null,"position":7,"is_corresponding":false},{"id":895587,"name":"Carmen Dressler","orcid":null,"position":8,"is_corresponding":false},{"id":1166445,"name":"Caesar G. Imperio","orcid":"0000-0002-7528-6723","position":9,"is_corresponding":false},{"id":921720,"name":"John Maurer","orcid":"0000-0003-2710-1963","position":10,"is_corresponding":false},{"id":734086,"name":"Heath D. Schmidt","orcid":"0000-0002-0646-5605","position":11,"is_corresponding":false},{"id":390354,"name":"Chongguang Chen","orcid":"0000-0003-3097-8176","position":12,"is_corresponding":false},{"id":925417,"name":"Kathryn Bland","orcid":null,"position":13,"is_corresponding":false},{"id":390356,"name":"Lee‐Yuan Liu‐Chen","orcid":"0000-0001-5206-9497","position":14,"is_corresponding":false},{"id":280661,"name":"Mathieu E. Wimmer","orcid":"0000-0002-4098-2497","position":15,"is_corresponding":false},{"id":824251,"name":"Andre Toussaint","orcid":"0000-0001-6559-9788","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:18:56.730121Z","pmid":"36711571","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}