Targeting the dopamine D3 receptor cannot influence continuous reinforcement cocaine self-administration in rats.

Recent studies point out the important role of dopamine D3 receptors in drug addiction. Therefore, D3 receptor ligands have been proposed as candidate medications for the treatment of cocaine dependence. The present study was designed to compare several dopamine D3 ligands of various selectivity in an animal model of drug-dependence, the cocaine self-administration paradigm. None of the doses of SB-277011 (5, 20 mg/kg), the most selective dopamine D3 antagonist to date, and the lower dose (12 mg/kg) of the moderately D3 selective antagonist U-99194A could influence the rate of self-administration. At the higher dose (24 mg/kg), U-99194A decreased the lever-pressing for cocaine. Both the dopamine D1 selective SCH-23390 (0.2, 0.1 mg/kg) and the dopamine D2 receptor preferring haloperidol (0.5, 0.2 mg/kg) increased the lever-pressing. Both the most dopamine D3 selective agonist PD-128907 (1.0 mg/kg) and the less selective 7-OH-DPAT (0.1, 0.5 mg/kg, s.c.) caused significant decrease in lever-pressing. At lower dose (0.2 mg/kg) PD-128907 was ineffective. The partial agonist BP-897 (1 mg/kg) evoked slight but significant increase in self-administration, while the lower dose (0.5 mg/kg) was ineffective. In all, in contrast to the dopamine D1 and D2 receptors acute inhibition or stimulation of the D3 receptor do not appear to exert considerable influence on the acute reinforcing effect of cocaine.