Kappa-opioid agonist U69593 potentiates locomotor sensitization to the D2/D3 agonist quinpirole: pre- and postsynaptic mechanisms

Neuropsychopharmacology. 2006 Sep;31(9):1967-81. doi: 10.1038/sj.npp.1300938. Epub 2005 Oct 12.

Abstract

To assess whether the development and expression of behavioral sensitization to the dopamine D2/D3 agonist quinpirole (QNP) is influenced by coadministration of the kappa opioid receptor agonist U69593, rats received every 3-4 days for a total of 10 treatments an injection of U69593 (0.3 mg/kg) together with an injection of either a postsynaptic (0.5 mg/kg) or a presynaptic dose of QNP (0.05 mg/kg); locomotor activity was measured after each treatment. Control rats were injected as appropriate with QNP, U69593, and vehicle/saline. Following chronic treatment, dose-response profiles to QNP were obtained to assess the expression of sensitization; the effect of U69593 on locomotor activity in animals already sensitized to QNP was also assessed. Results showed that cotreatment of U69593 with a postsynaptic dose of QNP doubled the speed and magnitude of sensitization to QNP, while U69593 cotreatment with a presynaptic dose of QNP switched the effects of QNP from locomotor depression to locomotor sensitization. However, U69593 cotreatment with a presynaptic dose of QNP changed a different set of measures of sensitization than did cotreatment with a postsynaptic dose of the dopamine agonist. Together, findings suggest that sensitization to QNP is not a unitary phenomenon but has components that are relatively independent, mediated by distinct pre- and postsynaptic mechanisms and modulated by kappa receptor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Analgesics / pharmacology*
  • Animals
  • Benzeneacetamides / pharmacology*
  • Data Interpretation, Statistical
  • Dopamine Agonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Male
  • Motor Activity / drug effects*
  • Pyrrolidines / pharmacology*
  • Quinpirole / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D2 / agonists*
  • Receptors, Dopamine D3 / agonists*
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Presynaptic / drug effects*
  • Synapses / drug effects

Substances

  • Analgesics
  • Benzeneacetamides
  • Dopamine Agonists
  • Pyrrolidines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Opioid, kappa
  • Receptors, Presynaptic
  • Quinpirole
  • U 69593