Journal of Neural Transmission

, Volume 64, Issue 3–4, pp 187–198 | Cite as

Sub-chronic administration of (−)-3-PPP and central dopamine receptor sensitivity changes

  • St. Hjorth
  • D. Clark
  • K. Svensson
  • A. Carlsson
  • O. Thorberg
Original Papers

Summary

The effects of sub-chronic treatment with (−)-3-PPP (8 mg/kg, s.c., b.i.d. for 21 days), a dopaminergic agent with mixed agonist/antagonist properties, were investigated by means of behavioural andin vivo biochemical methods. There was no change in basal locomotor activity and central dopamine (DA) synthesis after 24 hours withdrawal. A slight, though significant reduction of the locomotor suppressive effect and of the DA synthesis-stimulating effect of acute (−)-3-PPP challenge doses of 0.125 and 1.0 mg/kg (s.c.), respectively, were demonstrated in (−)-3-PPP-pretreated as compared to vehicle-pretreated rats. No change in either action was evident after acute challenge with 8.0 mg/kg (s.c.) of the drug. The plasma levels of (−)-3-PPP were virtually unchanged by pretreatment with active drug. The findings are discussed in terms of a modest down- and up-regulation of DA autoreceptors and postsynaptic receptors, respectively, induced by the subchronic (−)-3-PPP treatment.

Key words

(−)-3-PPP([−]-3-[3-hydroxyphenyl]-N-n-propylpiperidine) subchronic treatment rats dopamine receptors sensitivity changes 

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Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • St. Hjorth
    • 1
  • D. Clark
    • 3
  • K. Svensson
    • 1
  • A. Carlsson
    • 1
  • O. Thorberg
    • 2
  1. 1.Department of PharmacologyUniversity of GöteborgSweden
  2. 2.Research and Development Laboratories, Organic Chem. SectionAB AstraSödertäljeSweden
  3. 3.Lab. Neurophysiol., Ctr. for Cell BiologySinai Hospital of DetroitDetroitUSA

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