{"id":"1af40648-ca4d-5e6a-b57c-cff585593ce1","stable_key":"6660bba2-4fa0-590a-bf52-9803a24bea9f:d2-loss","predicate":"decreases_in_recorded_experiment","statement":"D2 receptor deletion reduced modafinil-induced wakefulness in mice; D1-like antagonist addition abolished the residual response.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"e74516d1-785a-55ba-b428-9e511bebbe17","mechanism_event_label":"D2 receptor deletion reduced modafinil-induced wakefulness in mice; D1-like antagonist addition abolished the residual response.","subject":{"id":"7ea1559f-0dcb-56c0-ab60-f392b77bb9c3","slug":"mouse-drd2","display_name":"Mouse dopamine D2 receptor / Drd2","entity_type_key":"protein"},"object":{"id":"2783faf9-3c82-5360-8540-e30f0f7310a1","slug":"mouse-wake-duration","display_name":"Mouse wake duration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e74516d1-785a-55ba-b428-9e511bebbe17","stable_key":"6660bba2-4fa0-590a-bf52-9803a24bea9f:d2-loss-event","event_type":"experimental_observation","label":"D2 receptor deletion reduced modafinil-induced wakefulness in mice; D1-like antagonist addition abolished the residual response.","description":"In mice, D2-receptor deletion reduced modafinil-induced wakefulness. 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[Qu et al., 2008](https://pubmed.ncbi.nlm.nih.gov/18716204/)","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7ea1559f-0dcb-56c0-ab60-f392b77bb9c3","slug":"mouse-drd2","display_name":"Mouse dopamine D2 receptor / Drd2","entity_type_key":"protein"},"role":"tested factor","stoichiometry":null,"state_label":"D2 deletion during modafinil exposure","sequence_order":0,"notes":""},{"entity":{"id":"2783faf9-3c82-5360-8540-e30f0f7310a1","slug":"mouse-wake-duration","display_name":"Mouse wake duration","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""},{"entity":{"id":"624e6a4b-f96d-5d12-8206-30d1e1715c26","slug":"modafinil","display_name":"Modafinil","entity_type_key":"drug"},"role":"drug challenge","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a46a6012-dff6-5f27-9595-ab254954e52f","slug":"mouse-d1-like-receptors","display_name":"Mouse D1-like dopamine receptor family","entity_type_key":"protein_family"},"role":"additional pharmacological manipulation","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary indexed abstract checked; full methods and figures not comprehensively reviewed.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"drug exposure","comparator":"Wild-type modafinil exposure","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"modafinil","display_name":"Modafinil","entity_type_key":"drug"}},{"dimension":"experimental_condition","value_text":"deletion","comparator":"Wild-type modafinil exposure","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"mouse-drd2","display_name":"Mouse dopamine D2 receptor / Drd2","entity_type_key":"protein"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"D2 deletion during modafinil exposure\", \"comparator\": \"Wild-type modafinil exposure\", \"endpoint\": \"D2 receptor deletion reduced modafinil-induced wakefulness in mice; D1-like antagonist addition abolished the residual response.\", \"effect_direction\": \"decrease\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"mouse-drd2\", \"state\": \"deletion\"}, {\"entity_slug\": \"modafinil\", \"state\": \"drug exposure\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Mouse receptor knockout and pharmacology; antagonist effects varied with modafinil dose.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"D2 receptor deletion reduced modafinil-induced wakefulness in mice; D1-like antagonist addition abolished the residual response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil. | 2008 | DOI 10.1523/jneurosci.1819-08.2008 | PMID 18716204 | https://pubmed.ncbi.nlm.nih.gov/18716204/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 73-73; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"86110312-5686-5c60-815e-00c8ef2585e1","evidence_kind":"source_excerpt","locator":"Lines 73-73","start_line":73,"end_line":73,"excerpt":"In mice, D2-receptor deletion reduced modafinil-induced wakefulness. Adding a D1-like antagonist abolished the remaining response. In wild-type mice, antagonist effects depended on modafinil dose. This supports dopamine-receptor involvement, not one fixed D1/D2 contribution across exposures. Pharmacological receptor-family blockade should not automatically become proof of a unique receptor subtype or anatomical location. [Qu et al., 2008](https://pubmed.ncbi.nlm.nih.gov/18716204/)","model_system":"Mouse receptor knockout and pharmacology; antagonist effects varied with modafinil dose.","directness":"reported_statement","verification_status":"source_recorded","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. 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