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Psychopharmacology

, Volume 143, Issue 3, pp 244–253 | Cite as

Dopaminergic mechanisms mediating the long-term expression of locomotor sensitization following pre-exposure to morphine or amphetamine

  • L. J. M. J. Vanderschuren
  • Anton N. M. Schoffelmeer
  • Arie H. Mulder
  • Taco J. De Vries
ORIGINAL INVESTIGATION

Abstract

The role of dopaminergic mechanisms in opiate- and psychostimulant-induced long-term locomotor sensitization was investigated. To that aim, rats were behaviourally sensitized with morphine or amphetamine and 3 weeks after cessation of treatment challenged with various direct and indirect dopamine agonists. Both morphine- and amphetamine-pretreated rats displayed sensitization of the locomotor effects of amphetamine, cocaine, and the selective dopamine reuptake inhibitor GBR-12909. Sensitization of the locomotor stimulant effects of the dopamine D2/D3 receptor agonist quinpirole was observed in amphetamine- but not morphine-pretreated rats. In contrast, morphine-, but not amphetamine-pretreated rats appeared hyposensitive to the locomotor inhibitory effects of a low, presumably D2-autoreceptor selective, dose of quinpirole. Neither pretreatment induced sensitization to the dopamine D1/D2 agonist apomorphine or the dopamine D1 agonist SKF-82958. In fact, the locomotor stimulant effects of SKF-82958 appeared to be decreased in animals pre-exposed to amphetamine. These results suggest that functional changes in presynaptic dopamine release mechanisms represent common neuroadaptations involved in the long-term expression of morphine- and amphetamine-induced locomotor sensitization. Presynaptic dopamine D2 and postsynaptic D2 and/or D3 receptors are differentially involved in the expression of morphine- and amphetamine-induced locomotor sensitization. In a parallel study, we report that all of the drugs that elicited sensitized locomotor responses in morphine- or amphetamine-pretreated rats caused reinstatement of previously extinguished heroin- or cocaine-seeking behaviour, respectively. Taken together, these data suggest a marked relationship between drug-seeking behaviour and drug sensitization.

Key words Behavioural sensitization Locomotor activity Morphine Amphetamine Dopamine D1 receptor Dopamine D2 receptor 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • L. J. M. J. Vanderschuren
    • 1
  • Anton N. M. Schoffelmeer
    • 1
  • Arie H. Mulder
    • 1
  • Taco J. De Vries
    • 1
  1. 1.Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Free University, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands e-mail: ljmj.vanderschuren.pharm@med.vu.nl, Fax: +31-20-4448100NL

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