Suppression of morphine-induced conditioned place preference by l-12-chloroscoulerine, a novel dopamine receptor ligand

The effect of 1-12-chloroscoulerine (I-CSL), a novel ligand with dual dopamine D-1 receptor agonistic and D-2 receptor antagonistic actions, on the development of morphine-induced conditioned place preference (CPP) was investigated in mice. Morphine (10 mg/kg)-induced place preference was dose dependently suppressed by coadministration of l-CSL (5, 10 and 20 mg/kg), which induced neither place preference nor place aversion when administered alone at a dose of 20 mg/kg. The D, receptor antagonist SCH23390 (0.1 mg/kg) suppressed, whereas the D2 receptor agonist (+/-)-2-(N-phenylethyl-N-propyl)-amino-5-hydroxytetralin (PPHT) (0.5 mg/kg) had no influence on the development of morphine-induced place preference. However, SCH23390 (0.1 mg/kg) did not affect, whereas PPHT (0.5 mg/kg) reversed the suppressive effect of I-CSL on the development of morphine-induced place preference. These results indicate that I-CSL suppresses the development of place preference of morphine by blocking D2 receptors. (C) 2003 Elsevier Science Inc. All rights reserved.