Studies On Effects And Mechanisms Of L-Tetrahydropalmatine On Oxycodone-Induced Dependence In Mice And Rats

Recent reports have indicated that l-tetrahydropalmatine (l-THP), which is an active component of Corydalis maybe have inhibited effects of morphine-induced dependence in rats and mice. The aim of our study is to investigate whether l-THP inhibits oxycodone-induced physical and psychological dependence in mice and rats, and find possible mechanisms of these effects. The results were followed:1. Studies on mechanisms of oxycodone-induced dependence were done. Few reports have been published about the intrinsic pharmacology of oxycodone. In our studies some kinds of oxycodone-induced dependence mode were used. Oxycodone induced physical dependence with naloxone-precipitated withdrawal signs in mice and rats. Locomotor activity was greatly increased and locomotor sensitivity was developed inducded by oxycodone in mice. The conditional place preference and self-administration was developed induced by oxycodone in rats. These results indicated that oxycodone had great potency of dependence in mice and rats. Competitive binding assay was carried on Chinese hamster ovarian cell separately transfeced with μ-,δ-, κ-opioid receptor to determine the receptor selectivity of oxycodone with non-selective antagonist ³H-diprenorphine. The results showed that the affinities of oxycodone to three types opioid receptors were similar, the number of IC₅₀ separately were 480.3±140.3, 144.7±36.1, 361±181.1 nmol/L, that of morphine are 1.32±1.29, 27.7±23.5, 16.9±12.9 nmol/L. These results indicate that the affinities of oxycodone to three types of opioid receptors are weaker than that of morphine, and oxycodone may be non-selective agonist.2. Studies on effects of l-THP on oxycodone-induced dependence in mice and rats. The results showed that l-THP per set didn't have potency of dependence, but could inhibit...