Blockade of morphine-induced place preference through the activation of κ-opioid receptors in mice

Abstract

The effects of pretreatment with the κ-agonists U-50,488H (U-50) and E-2078 on the morphine (MRP)-induced conditioned place preference (CPP) were examined in mice. Both U-50 (1 mg/kg, s.c.) and E-2078 (0.1 mg/kg, s.c.) induced a slight, non-significant place aversion. Pretreatment with U-50 (1 mg/kg) or E-2078 (0.1 mg/kg) abolished the MRP (3 mg/kg, s.c.)-induced CPP. In addition, MRP (3 mg/kg, s.c.) significantly increased the levels of the DA metabolites, DOPAC and HVA in the limbic forebrain (nucleus accumbens and olfactory tubercle). These effects were reduced by pretreatment with U-50. These results suggest that κ-agonists suppress the MRP-induced CPP, and that activation of κ-receptors could suppress the reinforcing effects of MRP which may be induced by enhanced DA transmission in the mesolimbic DA system.