Effects of CGS 10746B on hyperactivity and place preference induced by morphine

Behav Brain Res. 2001 Nov 29;126(1-2):23-32. doi: 10.1016/s0166-4328(01)00237-6.

Abstract

The effects of CGS 10746B, a dopamine release inhibitor, on spontaneous locomotor activity, morphine-induced hyperactivity, acquisition of conditioned place paradigm and morphine-induced conditioned place preference (CPP) was evaluated in male mice. In experiment 1, animals treated with CGS 10746B (0.5, 1, 2, 4, 8, 16, 24 and 32 mg/kg), morphine (40 mg/kg) or morphine (40 mg/kg) plus CGS 10746B (0.5, 1, 2, 4, 8, 16, 24 and 32 mg/kg) were placed in an actimeter during a period of 90 min. In experiment 2, animals treated with CGS 10746B (0.5, 1, 3 and 10 mg/kg), morphine (40 mg/kg) or morphine (40 mg/kg) plus CGS 10746B (0.5, 1, 3 and 10 mg/kg) were conditioned following a procedure unbiased in terms of initial spontaneous preference. In experiment 1, it was found that a decrease in spontaneous locomotor activity was produced between 0 and 45 min after administration of 24 and 32 mg/kg of CGS 10746B. In contrast, morphine induced hyperactivity between 45 and 90 min after administration. CGS 10746B reduced morphine-induced hyperactivity with doses of 2 mg/kg and higher. In experiment 2, CGS 10746B did not produce any effect on place conditioning but blocked morphine-induced CPP with doses from 1 mg/kg upwards. Our results confirm that an intact dopamine neurotransmission is critical for the manifestation of the motor and place preference conditioning effects of morphine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Association Learning / drug effects
  • Brain / drug effects
  • Brain / physiology
  • Choice Behavior / drug effects*
  • Conditioning, Classical / drug effects*
  • Dopamine / physiology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Male
  • Mice
  • Mice, Inbred Strains
  • Morphine / antagonists & inhibitors
  • Morphine / pharmacology*
  • Social Environment*
  • Thiazepines / pharmacology*

Substances

  • Antipsychotic Agents
  • Thiazepines
  • Morphine
  • CGS 10746B
  • Dopamine