{"doi":"10.1101/2022.06.10.493955","title":"Differential D <sub>1</sub> and D <sub>2</sub> receptor internalization and recycling induced by amphetamine <i>in vivo</i>","abstract":"Abstract The dopamine system plays a significant role in drug reward and the pathogenesis of addiction. Psychostimulant drugs acutely increase dopamine levels, triggering receptor internalization. In vitro data suggest that dopamine D 1 receptors (D 1 R) recycle, whereas D 2 receptors (D 2 R) degrade in response to activation. Yet, receptor fates in vivo remain unclear. This study bridges in vitro mechanisms and in vivo measurements of stimulant-induced modulation of receptor states using longitudinal multi-modal imaging combined with neuropharmacology. We demonstrate how repeated amphetamine administration differentially modulates D 1 R vs. D 2 R signaling in nonhuman primates over 24 hours using simultaneous positron emission tomography and functional magnetic resonance imaging. In contrast to predominantly inhibitory D 2 R signaling due to an initial amphetamine challenge, excitatory D 1 R functional signaling prevails three hours later, while D 2 Rs stay internalized. These results demonstrate differential externalization mechanisms of the D 1 R and D 2 R in vivo and a shift in receptor subtype activation after a dopamine surge.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303598,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":342699,"name":"Martin Schain","orcid":"0000-0003-2032-4312","position":1,"is_corresponding":false},{"id":996049,"name":"Helen P. Deng","orcid":null,"position":2,"is_corresponding":false},{"id":828468,"name":"Joseph B. Mandeville","orcid":"0000-0002-4113-5396","position":3,"is_corresponding":false},{"id":63233,"name":"Bruce R. Rosen","orcid":"0000-0002-8576-0839","position":4,"is_corresponding":false},{"id":473801,"name":"Christin Y. Sander","orcid":"0000-0001-6003-8615","position":5,"is_corresponding":false},{"id":805622,"name":"Hanne D. Hansen","orcid":"0000-0001-5564-7627","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:24.307938Z","pmid":null,"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":[]}