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Psychopharmacology

, Volume 112, Issue 2–3, pp 389–397 | Cite as

Chronic treatment with the D1 receptor antagonist, SCH 23390, and the D2 receptor antagonist, raclopride, in cebus monkeys withdrawn from previous haloperidol treatment

Extrapyramidal syndromes and dopaminergic supersensitivity
  • Henrik Lublin
  • Jes Gerlach
  • Linda Peacock
Original Investigations

Abstract

The effects of chronic treatment with dopamine (DA) D1 and D2 receptor antagonists were evaluated in eightcebus apella monkeys with mild oral dyskinesia after previous haloperidol treatment. SCH 23390 (D1 antagonist) was given daily to investigate the direct behavioural effect during long-term treatment and the subsequent supersensitivity to DA agonists. Raclopride (D2 antagonist) was investigated for comparison. All drugs were given subcutaneously. SCH 23390 and raclopride induced dystonic syndromes, catalepsy, sedation and reduced locomotor activity. The monkeys developed marked tolerance to the dystonic effect of SCH 23390, while they showed increased sensibility to the dystonic effect of raclopride. Baseline oral dyskinesia (24 h after injection) remained unchanged during D1 antagonist treatment, while it increased during D2 antagonist treatment. SCH 23390 induced supersensitivity to the oral dyskinesia- and grooming-inducing effects of SKF 81297 (D1 agonist) after 9 weeks, while the subsequent treatment with raclopride induced supersensitivity to the reactivity- and stereotypy-inducing effects of quinpirole (D2 receptor agonist) after 3 weeks. Because of the possibility of a carry-over effect (SKF 81297-induced oral hyperkinesia and grooming), other changes in raclopride-induced behaviours cannot be ruled out. The development of tolerance to the dystonic effect of SCH 23390 and the unchanged baseline oral dyskinesia during SCH 23390 treatment indicate an advantageous profile of side effects of DA D1 receptor blockade.

Key words

D1 receptors D2 receptors Extrapyramidal side effects Dopaminergic supersensitivity SCH 23390 Raclopride SKF 81297 Quinpirole Monkeys 

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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Henrik Lublin
    • 1
  • Jes Gerlach
  • Linda Peacock
  1. 1.Department P and Research Institute of Biological PsychiatrySt Hans HospitalRoskildeDenmark

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