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.
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.
Dias
Flávia Regina Cruz
FR
Behavioural Pharmacology Group, Laboratory of Animal Health, State University of North Fluminense, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, 28013-600, RJ, Brazil.
Carey
Robert J
RJ
Carrera
Marinete Pinheiro
MP
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
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D013469:Sulpiride; D001058:Apomorphine