Effect of (-)-DS 121 and (+)-UH 232 on cocaine self-administration in rats.

The novel dopamine autoreceptor antagonists (-)-DS 121 and (+)-UH 232 were tested for their ability to alter cocaine self-administration behavior in rats reinforced on a progressive ratio (PR) schedule. (-)-DS 121 (15 mg/kg) and (+)-UH 232 (30 mg/kg) produced significant decreases in breaking point. (-)-DS 121 produced variable results on rate of cocaine intake on an FR1 schedule, indicating that rate may on occasion be insensitive to changes in cocaine reinforcement. In animals previously trained to self-administer cocaine, (-)-DS 121 failed to maintain responding when substituted for cocaine. This profile suggests that (-)-DS 121 is a promising new candidate for the treatment of cocaine abuse.