title: Apomorphine-induced context-specific behavioural sensitization is prevented by the D1 antagonist SCH-23390 but potentiated and uncoupled from contextual cues by the D2 antagonist sulpiride.
abstract: BACKGROUND
  In the study of behavioural sensitization induced by dopamine agonists, D1 and D2 receptors have a critical, but a puzzling role.
  
  
  OBJECTIVE
  The objective of this study is to examine the effects of the D1 antagonist SCH-23390 and the D2 antagonist sulpiride given repeatedly alone or in combination with apomorphine upon apomorphine conditioning and sensitization.
  
  
  METHODS
  Apomorphine-induced (2.0 mg/kg) conditioning and sensitization were assessed following five paired/unpaired treatments. Sulpiride (10, 30 and 100 mg/kg) and SCH-23390 (0.01, 0.02 and 0.05 mg/kg) were administered alone or in combination with apomorphine. In experiment 1, the effect of 5 days of sulpiride and SCH-23390 treatments given alone were assessed on apomorphine reactivity. In experiment 2, sulpiride and SCH-23390 were co-administered with apomorphine for 5 days and subsequently, conditioning and sensitization tests were performed. In experiment 3, following five apomorphine treatment sessions, sulpiride and SCH-23390 were administered prior to the conditioning and sensitization tests.
  
  
  RESULTS
  SCH-23390 and sulpiride induced hyper-reactivity to apomorphine. SCH-23390 when given after the induction of apomorphine sensitization, blocked the expression of apomorphine sensitization. When given in combination with apomorphine, SCH-23390 blocked the apomorphine conditioning and sensitization, whereas low-dose sulpiride permitted conditioning and enhanced apomorphine sensitization and high-dose sulpiride blocked conditioning but permitted apomorphine sensitization. Both sulpiride doses transformed apomorphine sensitization from context-specific to context-independent sensitization.
  
  
  CONCLUSIONS
  The SCH-23390 findings are supportive of a critical role for D1 receptors in apomorphine effects whereas the sulpiride effects diminish the importance of conditioning and dopamine autoreceptor subsensitivity mechanisms in the mediation of apomorphine sensitization.
authors.affiliation: Behavioural Pharmacology Group, Laboratory of Animal Health, State University of North Fluminense, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, 28013-600, RJ, Brazil.
authors.forename: Flávia Regina Cruz
authors.initials: FR
authors.lastname: Dias
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Carey
authors.forename: Marinete Pinheiro
authors.initials: MP
authors.lastname: Carrera
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D003463:Cues; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D013469:Sulpiride; D001058:Apomorphine