Targeting the dopamine D 3 receptor cannot influence continuous reinforcement cocaine self-administration in rats

Abstract

Recent studies point out the important role of dopamine D 3 receptors in drug addiction. Therefore, D 3 receptor ligands have been proposed as candidate medications for the treatment of cocaine dependence. The present study was designed to compare several dopamine D 3 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 D 3 antagonist to date, and the lower dose (12 mg/kg) of the moderately D 3 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 D 1 selective SCH-23390 (0.2, 0.1 mg/kg) and the dopamine D 2 receptor preferring haloperidol (0.5, 0.2 mg/kg) increased the lever-pressing. Both the most dopamine D 3 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 D 1 and D 2 receptors acute inhibition or stimulation of the D 3 receptor do not appear to exert considerable influence on the acute reinforcing effect of cocaine.