Opioid peptides and their receptors play an important r ole in the pathophysiologic process of stroke. The concentration of endogenous o pioid peptides elevates, while the density of opioid receptors decreases in CNS during cerebral ischemia; on the other hand, opioids influence the development o f stroke through regulating the contraction of cerebral vessel, immuno-endocrin e system and neuroprotection against injury. Thus, drugs that regulate the opioi d system may be a new therapeutic approach for prevention and treatment of cereb ral ischemia.

As an important messenger molecule, NO exists in both peripheral and central nervous system (CNS). Recently, NO was proved to play a critical role in CNS, especially in synaptic plasticity. As a kind of retrograde messenger, it plays some roles in the induction and maintenance of LTP through activation of downstream pathway or molecules, such as NO-cGMP-PKG, ADPRT and C-FOS.

Aims To establish several behavioral paradigms to characterize the psychotropic effects of hallucinogens which ze-brafish was utilized as a model animal, and then to investigate the effects of potent hallucinogenic drugs on these models. Methods With the video record and track system, the behavior was recorded and quantified automatically. In the experiments, the bottom dwelling test, social behavior and mirror test were performed to test the hallucinogenic effects of drugs. Metham-phetamine (METH, 2 mg·L-1) and ketamine (20 mg·L-1) were selected as experimental challenges. The 30 min pre-treat-ment time was chosen based on our prior experience in zebrafish models. Results Compared to the normal group, in dwelling test, acute exposure of zebrafish to METH and ketamine de-creased transitions significantly, and in mirror reflection test, the drug-treated fish changed the preference for mirror zone, and ex-hibited aggressive for their mirror images. The pretreatment of METH and ketamine significantly reduced the contact durations, and the ketamine inhibited the contact frequency each other, the results indicated that the social interaction of zebrafish was im-paired. Conclusion The results confirm high sensitivity of ze-brafish models to hallucinogenic compounds with complex behav-ioral and physiological effects.

OBJECTIVE Toestablisharecombinantcelllinethatcanstablyexpressratpurinergic P2receptorP2X4(rP2X4R).METHODS ToconstructgreenfluorescentproteinandrP2X4recombinant plasmid (pEGFP-N1-rP2X4),lipofectamine was used to transfect pEGFP-N1-rP2X4 into human embry-onic kidney (HEK293)cells that were screened with G41 8 (1 g·L-1 ).The quantitative expression of rP2X4 receptor was verified by qRT-PCR and Western blotting analysis.Whole-cell patch clamp record-ing was used to investigate the function of the stably expressed rP2X4 receptor. RESULTS The sequence of plasmid pEGFP-N1-rP2X4 was verified by PubMed Blastn comparison.qRT-PCR and Western blotting analysis demonstrated that the expression of rP2X4 receptor in HEK293-pEGFP-N1-rP2X4 cell lines remained stable after 25 generations (P1 ,P3,P5,P10,P15,P20 and P25).Whole-cell patch clamp recording experiments showed that the rP2X4 receptor agonist,purine-5′-triphosphate (ATP,3.0 μmol·L-1 ),could activate rP2X4 receptors in HEK293-pEGFP-N1-rP2X4 cell lines.Specific activating current could be blocked by non-selective rP2X4 receptor antagonist TNP-ATP (30.0μmol·L-1).CONCLUSION rP2X4receptorisstablyexpressedinHEK293-pEGFP-N1-rP2X4cell line and maintains stable expression and function within 25 continuous generations.The establish ment of HEK293-pEGFP-N1-rP2X4 cell line can contribute to further investigations of the roles of rP2X4 receptors in neuropathic pain.

25% signified analgesic effect. Part II (the effect of agmatine on analgesic effect of morphine). Fifty-six animals with neuropathic pain were randomly divided into 4 groups ( n = 14 each) . Each group received NS or agmatine 20, 40 or 60 mg? kg-1 . 30 min later each group received either NS or morphine 1 mg?kg-1(n=7 each). PWT was measured and PMAP was calculated Part III (the effects of agmatine on the development of morphine tolerance). Morphine tolerance was incuced by morphine 10 mg?kg-1, 3 times a day for 5 days. Thirty-five animals with neuropathic pain were randomly divided into 5 groups ( n = 7 each): group A received NS: group B received NS + morphine; grouop C, D, E received agmatine 5, 10, 20 mg ? kg-1 + morphine 3 times a day for 5 days. PWT was measured on the 5th day and PMAP was calculated. Results PMAP of agmatine (40, 60 mg?kg-1 i.p.) and morphine (1 mg?kg-1 s.c.) were lower than 40% . Agmatine 60 mg?kg-1 increased the PMAP of morphine 1 mg?kg-1 to 84% compared with 34% for morphine alone (P

Psychostimulant is a type of psychoactive substances that stimulate central and peripheral nervous system as well as induce drug dependence.A series of studies indicate that monoamine especially dopamine plays an important role in behavior and drug dependence,moreover,dopamine transporter(DAT)controls homeostasis of dopamine in neuron and transmission of dopamine pathways.Thus DAT might play an important role in the reward and behavioral stimulation of psychostimulant.

Aim To investigate the changes in the expression of protein kinase C gamma (PKC?), phosphorylated cAMP response element binding protein(pCREB)and immediate-early gene(c-fos and c-jun) in the spinal cord in formalin-induced inflammatory pain and study the effect of agmatine on the changes of PKC? activation, phosphorylation of CREB and expression of c-fos and c-jun.Methods Rats were decapitated at 10, 20 min or 2 h after intraplantar injection of 50 ?l 5% formalin and L_4, 5 spinal cords were dissected. Immunohistochemistry and western blotting analyses were used to observe the expression of PKC?, pCREB, c-fos and c-jun in the spinal dorsal horn and the effect of agmatine on the changes of their expression. Results Unilateral peripheral inflammation induced PKC? activation and CREB phosphorylation bilaterally while c-fos and c-jun expression ipsilaterally in rat spinal cord. PKC activity increased in membrane fractions with unchanged levels in the cytosolic fractions. Pretreatment intraperitoneally with 160 mg?kg-1 agmatine 15 min before inflammation significantly inhibited the activation of PKC? in the membrane fraction, suppressed the phosphorylation of CREB and the expression of c-fos and c-jun. Conclusion The mechanism of the analgesic effect of agmatine may be associated with inhibiting PKC? activation in the plasma membrane, CREB phosphorylation, c-fos and c-jun up-regulation which play roles in the hyperalgesia with peripheral inflammation.

OBJECTIVE:To study the bioequivalence of 2 kinds of Losartan potassium tablets in healthy volunteers. METHODS: A single oral dose of test tablet 100 mg and reference tablet 100 mg were given to 20 healthy volunteers in randomized crossover study. The plasma concentrations of losartan and its metabolite EXP3174 were determined by LC-MS. The pharmacokinetic parameters were calculated and bioequivalence of 2 kinds of tablets was evaluated. RESULTS: Main pharmacokinetic parameters of Losartan of test tablets vs. reference tablets were as follows: Cmax(534.230?238.642) ng?mL-1 vs.(520.020?226.800) ng?mL-1; tmax(1.401?0.946)h vs.(1.334?0.750)h; AUC0～36(871.177?232.315) ng?h?mL-1 vs. (773.030?252.209) ng?h?mL-1; pharmacokinetic parameters of metabolite EXP3174 of test tablets vs. reference tablets were as follows: Cmax (1 294.000?387.815) ng?mL-1 vs.(1 140.900?317.615)ng?mL-1;tmax(2.667?1.144)h vs.(2.734?1.162)h;AUC0～36(6 267.905?1 350.300)ng?h?mL-1 vs.(5 719.411?1 127.725) ng?h?mL-1; AUC0～∞(6 316.605?1 343.048)ng?h?mL-1 vs. (5 755.335?1 138.358) ng?h?mL-1. The relative bioavailability of test tablet was (116.6?24.3)%. CONCLUSION: 2 kinds of Losartan potassium tablets are bioequivalent.

Opioid receptors, as an important member of G protein coupled receptors (GPCR), are the binding targets of endogenous opioid peptides and exogenous opiates. The activation of opioid receptors influences the nervous system, immune physiology and endocrine system. However, prolonged activation of opioid receptors is likely to produce opioid tolerance, leading to opioid addiction. Receptor endocytosis and sorting into the recycling pathway contribute to recovery of cellular opioid responsiveness. Recent studies have revealed that GPCR can be modulated by ubiquitination which plays a unique roles in governing GPCR trafficking. Moreover, ubiquitination of the opioid receptors (μ, κand δ) is increased after stimulation of most opioid agonists. Mutation of the ubiquitin sites affects the internalization and degradation of opioid receptors, which contributes to changes in signal pathways and regulation of opioid receptors. ln this paper, ubiquitination of opioid receptors and the fundamental role of ubiquitination in trafficking of opioid receptors are reviewed.

Voltage-gated sodium channels (NaV1.1-NaV1.9) play important roles in the generation and maintenance of electrical excitability. NaV1.7 is preferentially expressed in peripheral somatic sensory neurons and sympathetic ganglion neurons. ln humans, gain-of-function mutations of SCN9A gene, which encodes NaV1.7, cause inherited neuropathic pain, whereas loss-of-function mutations result in a congenital indifference to pain without motor, cognitive and cardiac deficits. The effects of some analge-sics are associated, at least in part, with the NaV1.7 and selective NaV1.7 inhibitors have also been demonstrated to be analgesic in animal models. NaV1.7 has emerged as a potential target for the treat-ment of pain.