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The α2-adrenoceptor antagonist atipamezole reduces the development and expression of d-amphetamine-induced behavioural sensitization

Naunyn-Schmiedeberg's Archives of Pharmacology volume 367, pages 274–280 (2003)Cite this article

Abstract

The possible effect of atipamezole, a potent and specific α2-adrenoceptor antagonist, on the development and expression of d-amphetamine-induced behavioural sensitization was evaluated in mice. Male (C57Bl/6J) mice were given daily doses of d-amphetamine (2 mg/kg). In addition, groups of mice received injections of atipamezole (0.3 or 1 mg/kg) 20 min before d-amphetamine or vehicle administration. Idazoxan (1 mg/kg) was used in some experiments to extend the results to other α2-adrenoceptor antagonists. Challenge doses of d-amphetamine were administered to the mice on days 7–9 to evaluate the effects of α2-adrenoceptor antagonists on the d-amphetamine sensitization, evidenced by increased locomotor activation.

Mice treated repeatedly with d-amphetamine developed strong locomotor sensitization that was reduced by pretreatment with α2-adrenoceptor antagonists. Acute atipamezole at both doses attenuated the expression of d-amphetamine-induced sensitization. Atipamezole at 1 mg/kg alone had no effect on locomotor activity, but the lower dose (0.3 mg/kg) increased locomotor activity after repeated administration.

These results indicate that α2-adrenoceptor antagonists modulate the actions of d-amphetamine in a manner not explicable by their enhancing actions on noradrenaline and dopamine release, and may thus provide a novel approach to the treatment of motor complications caused by dopaminergic agents, such as dyskinesias, and perhaps also drug dependence.

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Acknowledgements

This study was supported by Orion Corporation, Orion Pharma and by the Sigrid Juselius foundation.

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Affiliations

  1. Department of Pharmacology and Clinical Pharmacology, University of Turku, 20520, Turku, Finland

    Juuso Juhila, Aapo Honkanen, Esa R. Korpi & Mika Scheinin

  2. Orion Corporation, Orion Pharma, 20101, Turku, Finland

    Juuso Juhila, Antti Haapalinna, Jouni Sirviö & Jukka Sallinen

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  1. Juuso Juhila
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  2. Antti Haapalinna
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  3. Jouni Sirviö
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  4. Jukka Sallinen
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  7. Mika Scheinin
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Correspondence to Mika Scheinin.

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Juhila, J., Haapalinna, A., Sirviö, J. et al. The α2-adrenoceptor antagonist atipamezole reduces the development and expression of d-amphetamine-induced behavioural sensitization. Naunyn-Schmiedeberg's Arch Pharmacol 367, 274–280 (2003). https://doi.org/10.1007/s00210-003-0695-6

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  • DOI: https://doi.org/10.1007/s00210-003-0695-6

Keywords

  • α2-Adrenoceptors
  • d-amphetamine
  • Locomotor activity
  • Behavioural sensitization