The dopamine D1 receptor agonist and D2 receptor antagonist LEK-8829 attenuates reinstatement of cocaine-seeking in rats

Various dopaminergic drugs have been studied for their efficacy in the treatment of cocaine addiction. Pretreatment with either selective dopamine D1 receptor agonists or selective dopamine D2 receptor antagonists prevents reinstatement of cocaine-seeking in animal models of drug craving and relapse. We tested a novel ergoline derivative with combined D1 agonistic and D2 antagonistic effects, 9,10-didehydro-N-methyl-N-(2-propynyl)-6-methyl-8β-aminomethylergoline bimaleate (LEK-8829), for its effects on cocaine-seeking in the intravenous cocaine self-administration model in rats. Pretreatment with systemic injections of LEK-8829 attenuated reinstatement of cocaine-seeking induced by cocaine priming injections and diminished cocaine intake in cocaine self-administration sessions. LEK-8829 itself did not induce reinstatement of cocaine-seeking and did not maintain intravenous self-administration. The results of our study indicate that LEK-8829 is a candidate medication for the treatment of cocaine craving in cocaine addiction.