Corydaline and l-tetrahydropalmatine attenuate morphine-induced conditioned place preference and the changes in dopamine D2 and GluA1 AMPA receptor expression in rats.

Corydalis is a Chinese herb that has been used in China for hundreds of years for analgesic and other purposes. Corydaline and l-tetrahydropalmatine (l-THP) are the main active ingredients of Corydalis. This study was aimed to study the potential utility of corydaline and l-THP in the treatment of opioid abuse and addiction and explore the possible mechanisms underlying their pharmacological actions. Conditioned place preference (CPP) was used to evaluate the rewarding effects of morphine and Western-blot immunoreactive assays were used to evaluate morphine-induced changes in dopamine D2 receptor and GluA1 AMPA receptor and GluA2 AMPA receptor expression in the brain of rats. Systemic administration of corydaline (5 mg/kg, i.p.) or l-THP (1.25, 2.5,5 mg/kg) significantly inhibited the acquisition and expression of morphine-induced CPP in a dose-dependent manner. Corydaline or l-THP alone, at the same doses, failed to produce CPP or conditioned place aversion, and didn't affect locomotor activity. We then examined the expression of dopamine D2 receptor and GluA1 AMPA receptor and GluA2 AMPA receptor subunit expression in rats after acquisition of morphine-induced CPP. We found that repeated administration of morphine produced a significant reduction in dopamine D2 receptor expression in the prefrontal cortex, hippocamps, and striatum, while an increase in the striatal GluA1 AMPA receptor expression. Pretreatment with corydaline or l-THP blocked morphine-induced dopamine D2 receptor down-regulation and GluA1 AMPA receptor up-regulation in these brain regions. Corydaline and l-THP may have therapeutic potential in prevention and treatment of opioid abuse and addiction. The underlying mechanisms may be related to their antagonism on morphine-induced changes in dopamine and glutamate transmission in the brain.