Cocaine sensitization prevents the hypolocomotor effects of high but not low doses of PD 128,907

Eric P.M. Prinssen, Wouter Koek, Mark S. Kleven

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

In this study we examined the effects of the preferential dopamine D3 receptor agonist S(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol (PD 128,907) on locomotion in mice sensitized to cocaine. In mice repeatedly treated with saline, PD 128,907 induced hypoactivity over a wide dose range (0.01-40 mg/kg); however, after repeated treatment with 40 mg/kg cocaine, higher doses of PD 128,907 (2.5-40 mg/kg) no longer induced hypoactivity whereas the effects of lower doses (0.01-0.16 mg/kg) were not altered. Because lower doses of PD 128,907 are thought to induce hypoactivity via activation of dopamine D3 receptors, the present data suggest that, under conditions where cocaine induces marked sensitization to its locomotor effects, the sensitivity of these receptors is not altered. In contrast, because higher doses of PD 128,907 can activate dopamine D2 receptors, it is conceivable that apparent cross-sensitization to its dopamine D2 receptor agonist properties is responsible for the lack of hypolocomotor effects at high doses. Overall, the results indicate that altered dopamine D3 receptor sensitivity does not play an important role in the expression of cocaine-induced sensitization. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)19-22
Number of pages4
JournalEuropean Journal of Pharmacology
Volume355
Issue number1
DOIs
StatePublished - Aug 14 1998
Externally publishedYes

Keywords

  • Cocaine
  • Dopamine
  • Dopamine D receptor
  • Dopamine reuptake inhibitor
  • Hypolocomotion
  • Locomotion
  • PD 128,907
  • Reverse tolerance
  • Sensitization

ASJC Scopus subject areas

  • Pharmacology

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