Effect of Corydalis Rhizoma and L-tetrahydropalmatine on dopamine system of hippocampus and striatum in morphine-induced conditioned place preference rats / 中国中药杂志

To investigate the effects of Corydalis Rhizoma and L-tetrahydropalma-tine (L-THP) on the levels of dopamine neurotransmitter (DA), dopamine transporter (DAT) and the second dopamine receptor (D2R) in learning and memory-related brain areas, hippocampus and striatum, the DA, DAT and D2R were detected in conditioned place preference (CPP) rats suffered from morphine. And comparation the degree of similarity and consistency of the pharmacological effects was also studied. The rats were trained in black compartments and white ones (drug-paired compartment) with the increasing doses of morphine for 10 days (hypodermically injected from 10 mg•kg⁻¹ to 100 mg•kg⁻¹). Models of CPP were validated in those psychological dependence rats after 48 h training. The dopamine contents were detected as soon as the materials of hippocampus and striatum are harvested from rats of NS control group and model group. The DAT and D2R levels are measured by Western blot. The high, medium and low dose group of Corydalis Rhizoma are given Corydalis Rhizoma 2, 1, 0.5 g•kg⁻¹ water extraction liquid respectively (which contains L-THP were 0.274, 0.137 and 0.137 mg respectively), and the high, medium and low dose group of L-THP were given L-THP 3.76, 1.88, 0.94 mg•kg⁻¹ lavage treatment respectively, NS treatment group were lavaged normal saline for 6 days and they were killed after test of CPP, again tested DA levels and expression of DAT and D2R similar to the front of materials. The reduction effects of CPP were observed in the groups of both Corydalis Rhizoma (2, 1 g•kg⁻¹) and L-THP (3.76, 1.88 mg•kg⁻¹) subjected to medicine for 6 days (P<0.01). Compared with the NS treatment group and the model group, the higher values including in the contents of neurotransmitter dopamine were detected of hippocampus and striatum (P<0.01, P<0.05), the DAT and D2R protein expression of Corydalis Rhizoma (2, 1 g•kg⁻¹) and L-THP (3.76, 1.88 mg•kg⁻¹) increased in hippocampus and striatum (P<0.01). Learning and memory-related brain regions hippocampus and striatum was another neuroanatomical sites of action in the treatment of mental dependence of fumarate and L-THP, its mechanism was related to lowering its elevated DA neurotransmitter levels, and increasing the expression of DAT and D2R. Corydalis Rhizoma could be play 14-times roles in effect of L-THP. The similar effects were observed on the neurotransmitter dopamine, DAT and D2R in learning and memory-related brain areas, hippocampus and striatum of the morphine- dependent rats.

Study on effects of Corydalis yanhusuo and L-THP on dopamine of reward circuitry in conditioned place preference rats and comparison / 中国中药杂志

<p><b>OBJECTIVE</b>To study and compare the effect of Corydalis yanhusuo and L-THP on dopamine neurotransmitter and D2 receptor of reward circuitry in various cerebral areas of conditioned place preference model rats and the comparison of their effects.</p><p><b>METHOD</b>The CPP model was established by injecting morphine in rats with increasing doses for 10 days. The initial dose of 10 mg x kg(-1), and the final dose of 100 mg x kg(-1), with 10 mg x kg(-1) increased each day. At 48 h after the final training, CPP was adopted to detect the successful establishment of the model. On the same day (12 d), they were orally administered with 2, 1, 0.5 g x kg(-1) C. yanhusuo (containing 0.153, 0.077 and 0.038 mg L-THP) and L-THP (3.76, 1.88, 0.94 mg x kg(-1)) for six days. On 18 d, CPP test was performed again. Next day, HPLC was adopted to determine the content of dopamine neurotransmitters of reward circuitry in VTA-NAc-PFC; Immunohistochemistry and Western blotting were adopted to detect the expression of D2 receptors.</p><p><b>RESULT</b>Compared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76, 1.88 mg x kg(-1)) groups showed that rats stayed in a notably shorter period in white boxes (morphine-accompanied boxes) (P < 0.01 or P < 0.05), and revealed a remarkably lower dopamine content in VTA, NAc and PFC and the significant increase in the expression of D2 receptor (P < 0.01 or P < 0.05).</p><p><b>CONCLUSION</b>The down-regulation of the increased dopamine content in reward nervous circuitry and the up-regulation of the expression of D2 receptor may be one of mechanisms of C. yanhusuo and L-THP in accelerating the recession of morphine's CPP effect Regarding the inhibition of morphine's CPP effect and the effect on dopamine system, the effect of C. yanhusuo traditional Chinese medicine containing one-fold L-THP monomer is equal to that of the independent application of around 24-fold L-THP monomer.</p>

Study on acting mechanism of anti-morphine conditioned place preference between aqueous extract of Corydalis yanhusuo and L-THP and comparison of their effects / 中国中药杂志

<p><b>OBJECTIVE</b>To study the acting mechanism of anti-morphine conditioned place preference (CPP) between aqueous extract of Corydalis yanhusuo and L-THP and compare their effects.</p><p><b>METHOD</b>The CPP model was established by injecting morphine in rats with a increasing dose for 10 days, with the initial dose of 10 g x kg(-1) and the final dose of 100 g x kg(-1), 10 mg x kg(-1) was increased each day, thus 100 mg x kg(-1) was injected by d 10. Having been treated with differential doses (2, 1 and 0.5 g x kg(-1)) of C. yanhusuo (containing L-THP: 0.153, 0.077 and 0.038 mg x kg(-1) respectively) and L-THP (3.76, 1.88 and 0.94 mg x kg(-1)) for six days, the CPP effect in rats was detected. Both colorimetry and immunohistochemistry methods were adopted to detect the content of glutamate neurotransmitter in each brain region and the expression of NR2B in VTA-NAc-PFC neuroanatomical circuit.</p><p><b>RESULT</b>Compared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76 and 1.88 mg x kg(-1)) groups showed a notably shorter retention period of rats in white boxes (morphine-accompanied boxes) (P < 0.05 or P < 0.01) and remarkably lower glutamic acid content in VTA, NAc and PFC and NR2B expression.</p><p><b>CONCLUSION</b>Both C. yanhusuo and L-THP can substantially inhibit the effect of morphine CPP, reduce the increasing glutamic acid content in VTA-NAc-PFC neuroanatomical circuit and down-regulated NR2B expression, which may be one of mechanisms on reducing the effect of morphine CPP. C. yanhusuo preparations containing L-THP (1 x ) showed 24-fold effect of L-THP monomer of single application in terms of the behaviouristics of inhibitory effect on CPP as well as the similarity in terms of transmitter glutamic acid of in VTA-NAc-PFC neuroanatomical circuit and pharmacological mechanism of NR2B.</p>

Changeable expressions of glutamate neurotransmitter and NR2B in neuroanatomical circuit of ventral temental area, nucleus accumbens and prefrontal cortex in morphine-psychic dependent rats / 中华神经医学杂志

Objective To explore the mechanism of opioid-psychic dependence involving the aspects of pre-receptor and receptor by observing the changeable expressions of glutamate neurotransmitter and NR2B of N-methyl-D-aspartic acid (NMDA) receptor in the neuroanatomical circuit of ventral temental area, nucleus accumbens and prefrontal cortex (VTA-Nac-PFC) of rats subjected to morphine-induced conditioned place preference (CPP). Methods The models of CPP were validated by escalating doses of morphine in rats (n=16). The colorimetry and immunohistochemistry ways were applied to detect the contents of glutamic acid and the expression level of NR2B in VTA, Nac and PFC. Results As compared with those in the control group physiological saline), the prolonged detention time of white compartment in the model group was notably observed (P<0.05), and increased content of glutamic acid and expression level of NR2B in fields of VTA, Nac and PFC in the model group were significantly detected (P<0.05). Conclusion Increased level of giutamic acid and expression level of NR2B in nuroanatomieal circuit of VTA, Nac and PFC could play key roles in inducing morphine-psychic dependent rats.