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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

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Abstract

Rationale

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.

Conclusion

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.

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Acknowledgements

This research was supported by UENF, VA Merit Review Grant and NIDA Grant R01 05366. F. R. C. D. was a recipient of a fellowship from UENF, Brazil. We thank Gina Nunes Teixeira for technical assistance and Dr. Richard Ian Samuels for revision of the text. The experiments were performed in compliance with the recommendations of Brazilian Society of Neuroscience and Behaviour (SBNeC), which are based on the US National Institutes of Health Guide for Care and Use of Laboratory Animals.

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Authors and Affiliations

  1. Behavioural Pharmacology Group, Laboratory of Animal Health, State University of North Fluminense, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, 28013-600, RJ, Brazil

    Flávia Regina Cruz Dias & Marinete Pinheiro Carrera

  2. Research and Development (151), VA Medical Center and SUNY Upstate Medical University, 800 Irving Avenue, Syracuse, NY, 13210, USA

    Robert J. Carey

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  1. Flávia Regina Cruz Dias
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  2. Robert J. Carey
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  3. Marinete Pinheiro Carrera
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Correspondence to Marinete Pinheiro Carrera.

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Dias, F.R.C., Carey, R.J. & Carrera, M.P. 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. Psychopharmacology 209, 137–151 (2010). https://doi.org/10.1007/s00213-009-1768-0

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