Dopamine D3 receptor ligands show place conditioning effect but do not influence cocaine-induced place preference.

The importance of dopamine D3 receptors in reward related processes, especially in cocaine addiction, has been investigated extensively. However, in the reported studies a combination of different experimental conditions and different ligands have been used which renders the interpretation and comparison of the diverse results extremely difficult. Here, we report one comparative study investigating a wide range of dopamine D3 receptor ligands in one model of cocaine abuse: the place conditioning paradigm in rats. Of the antagonists tested, the moderately D3 selective nafadotride and the more selective SB-277011 did not produce any place conditioning effect while U-99194A caused place-preference. The most D3 selective agonist PD-128907, the less selective 7-OH-DPAT and the moderately selective partial agonist BP-897 all caused significant place aversion. None of the compounds influenced the cocaine-induced place preference. Results suggest the D3-preferring agonists could affect the reward mechanisms of the brain, however, modulation of D3 receptor function does not appear to be a significant mechanism for modifying the place conditioning effect of cocaine. Copyright 2003 Lippincott Williams & Wilkins