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Objective To investigate the effects of Ligustilide on the withdrawal syndromes syn-dromes and monoamine neurotransmitters of hypothalamus and nucleus accumbens in morphine-dependent rats. Methods Totally 60 SD rats were divided into control group,model group,clonidine group and Ligust-ilide high(80 mg/kg),medium(40 mg/kg) and low(20 mg/kg) dose group according to the random number table with 10 in each group. Rats were given in gradual increasing doses of morphine to produce physical de-pendence. Morphine withdrawal syndrome was precipitated by naloxone and withdrawal symptoms were evalu-ated by Ryuta Tomoji score. The level of norepinephrine ( NE), dopamine ( DA) and 5-hydroxytryptamine (5-HT) in rats were tested with enzyme-linked immunosorbent assay(ELISA). Results The total score of somatic withdrawal syndromes in the control group,model group,clonidine group and Ligustilide low,medium and high dose group were 0,(31. 83±7. 33),(17. 92±6. 88),(25. 58±5. 99),(19. 88±4. 82) and (16. 75 ±4. 01) . Compared with the model group,the morphine withdrawal syndromes scores of Ligustilide low,me- dium and high dose groups and clonidine group were reduced(all P<0. 05). The level of NE,DA and 5-HT in hypothalamus and nucleus accumbens were increased compared with that of control group. Compared with the model group,the level of NE,DA and 5-HT in hypothalamus and nucleus accumbens of Ligustilide low, medium and high dose groups and clonidine group were significantly reduced (P<0. 05). Conclusion Ligu-stilide can effectively alleviate the symptoms in morphine-withdrawal rats,which may be related to the inhibi-tion of excessive release of monoamine neurotransmitters in hypothalamus and nucleus accumbens.
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Objective To explore the effects of angelica naphtha on the withdrawal signs and norepinephrine neurotransmitter in uorphine-dependent rats.Methods 72 SD rats were randomly divided into control group,model group,clonidine group and three angelica naphtha groups (80,40 and 20 mg/kg).Rats were received gradualy increasing doses of morphine to produce physical dependence.Withdrawal symptoms were evaluated by Ryuta Tomoji score.The level of norepinephrine and normetanephrine(NMN) were tested by enzyme-linked immunosorbent assay(ELISA).Results The scores of withdrawal signs were (4.00± 3.29),(30.13±4.41),(18.96± 4.43),26.04±4.13),(22.33±4.60) and (19.00±3.47),respectively.The morphine withdrawal signs were reduced by angelica naphtha in a dose-dependent manner(P＜0.01),also significantly reduced the level of NE and NMN and the ratio of NMN/NE in the nucleus ceruleus and prefrontal cortex(all P＜0.01).Conclusion Angelica naphtha alleviates the withdrawal synlptons in morphine-dependent rats,which may be related to the inhibition of excessive turnover of norepinephrine neurotransmitters in the nucleus ceruleus and prefrontal cortex.
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Objective To study the effect of Danggui Buxue Decoction on red cell immune function in mice with morphine abstinence syndrome. Methods 50 mice were randomly divided into normal group,positive control group, high, medium, low dose group,Hindlimb injection of morphine in morphine dependent mice model was established.Erythrocyte membrane were measured in five groups of mice micro viscosity, erythrocyte deformation index; Determination of red cell immune complex rosette rate using the method (CIC), red cell C3b receptor rosette rate;and to observe the five group of regulator factor enhance rate (RFER) and immune adherence inhibitor factor (RFIR) levels.Results Erythrocyte membrane microviscosity in model group were significantly higher than those in normal group, medium group and low group (P<0.05),red cell deformability index was lower than that of normal group, drug medium group and drug group low (P<0.05).Drug high group and medium group,immune complex rosette rate lower than in model group(P<0.05), C3b receptor rosette rate was significantly higher than that in the model group (P<0.05).Conclusion Low dose group and high dose group Danggui Buxue Decoction raises the red cell immune function in morphine withdrawal mice, improves the withdrawal symptoms, rapids rehabilitation of the body, has good clinical value.
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AIM:To observe the effects of cholecystokinin octapeptide (CCK-8) and its receptor antagonists on cAMP response element binding protein ( CREB) and phosphorylated CREB ( pCREB) expression in frontal cortex and hippocampus of morphine withdrawal rats , which aim to explore the post-receptor mechanism through which CCK-8 regu-lates morphine withdrawal .METHODS: After the morphine dependence and naloxone-precipitated withdrawal animal models were established, the effects of CCK-8, L-364718 (CCK1 receptor antagonist) and LY-288513 (CCK2 receptor an-tagonist) pretreatment on CREB and pCREB expression in frontal cortex and hippocampus were observed by Western blot -ting and immunohistochemistry .RESULTS:In rat frontal cortex neuron , CREB was expressed in both cytoplasm and nu-cleus, but pCREB was only highly expressed in the nucleus .In the pyramidal cell layer of hippocampal CA 1 region, CREB showed high expression in the cytoplasm and low expression in the nucleus , while pCREB was only expressed in the nu-cleus.No obvious change of CREB was observed after either chronic morphine treatment or naloxone withdrawal .The pCREB expression was increased after chronic morphine treatment and further increased after naloxone withdrawal .Com-pared with the withdrawal group , chronic pretreatment with CCK-8, L-364718 and LY-288513 had no effect on CREB expression in the frontal cortex , but obviously decreased the pCREB expression .In the hippocampus , pretreatment with L-364718 and LY-288513 decreased CREB and pCREB expression , but only the pCREB expression was decreased after CCK-8 treatment.CONCLUSION:CCK-8 and CCK receptor antagonists may alleviate morphine withdrawal symptoms by regulating CREB , with specificity in different brain regions .
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Objective To research the mechanism of electroacupuncture(EA) improving morphine abstinence syndrome in rats.Methods The model of the rat with physical morphine abstinence syndrome was established.The expression of ?-opioid receptor mRNA in the brain tissue of morphine withdrawal rats was examined by RT-PCR,and effects of EA at Zusanli(ST36) on the body weight and expression of ?-opioid receptor mRNA of morphine withdrawal rat were observed.Results The body weight of the EA group was increased compared with the morphine abstinence group(P
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Objective To investigate the contents of cAMP and cGMP in the central nervous system in morphine dependent and withdrawal rats.Methods A physical morphine dependent model in rats was established by subcutaneous injection of morphine in gradually increasing doses.The cAMP and cGMP contents in the brain regions were determined by radioimmunoassay.Results Compared with control group,morphine dependence could significantly decrease the cGMP content or profoundly increase the cAMP content and the cAMP/cGMP ratio in rat striatum,diencephalons,midbrain,pons and hippocampus,but these changes described above were not detected in cerebellum.Compared with morphine dependent group,naloxone induced withdrawal could significantly decrease the cGMP contents or increase the cAMP contents and the cAMP/cGMP ratio in striatum and hippocampus,but these changes described above were not observed in the other regions.Conclusion The changes of the cAMP and cGMP contents may be one of the important molecular mechanisms leading to morphine dependence and abstinence.
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Objective To observe effect of Compound Ruikangxin Capsula(CRC) on anxiety-like symptoms of morphine-withdrawal rats and investigate its mechanism.Methods The elevating doses were applied to validating anxiety-like behavior in SD male rats with sc morphine for 10 d.Treatments with ig administration of CRC(100,200,and 300 mg/kg) and buspirone(15 mg/kg) were performed during 1—3 d morphine withdrawal(twice every day).The plus elevated maze was applied to validating anxiety-like symptom in rats.The expression levels of synaptophysin were detected on hippocampus in groups by immunohistochemitry 72 h after sc morphine.Results As compared with the control group,animals treated with CRC(200 and 300 mg/kg) and buspirone had higher ratio of entry into open arm (P
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Objective: To observe the effect of phophodiesterase 5 (PDE5) inhibitor, sildenafil on morphine withdrawal symptoms in mice. Method: A physical morphine dependent model in mice was established by subcutaneous injection of morphine in gradually increasing doses. After interperitoneal injection of naloxone (0.2mg/kg), withdrawal symptoms including jumping in 15 min, jumping latent period and weight loss were scored to evaluate the response intensity of morphine withdrawal. The effect of sildenafil (15mg/kg, 30mg/kg and 60mg/kg) was observed. Using nitrate reductase method to detect NO (nitric oxide) content in the blood and brain of mice. Result: Morphine withdrawal symptoms were aggravated by 3 different dosage of sildenafil and assumed good dose-dependent manner. NO content in blood increased after 30mg/kg sildenafil, which had no effect on NO content in brain of mice. Conclusion: Morphine withdrawal symptoms can be aggravated by sildenafil, which has also influence on blood content of NO, but has no influence on NO content in brain.
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Objective: To observe the effect of urapidil (agonist of 5-HT 1A receptor ) on morphine withdrawal syndrome Method: A physical dependent model in mice was established by subcutaneous injection of quantitative morphine The intensity of withdrawal syndrome was evaluated by observing jumping latency, jumping times and lose of body weight after intraperitoneal injection of naloxone (5 mg/kg) The effect of urapidil was observed after intraperitoneal injection it with 3 different dosages (100, 200, 400 mg/kg) Contents of NO in plasma and brain tissue were measured by nitrate reduction method Results: Morphine withdrawal syndrome was inhibited by urapidil at any dosage Content of NO in brain tissue reduced by urapidil 400 mg/kg, while plasma NO increased Conclusion: Urapidil inhibits morphine withdrawal syndrome in mice, increase the content of NO in their brain tissue
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Objective To study the relation between the level of central N-methyl-D-aspartate (NMDA) receptor system and the degree of morphine withdrawal syndrome in rats. Methods We established the morphine-dependence model in rats,stimulated addiction by naloxone after intracerebroventricular injection of glutamic acid/ketamine/MK-801,and then observed the effects on rats' morphine withdrawal syndrome. Results Glutamic acid significantly raised the behavior scores of teeth chattering,wet shakes,writhing,penis licking and weight loss,while ketamine and MK-801 decreased the scores. Conclusion Changes of central NMDA system obviously affect morphine withdrawal syndrome in rats,which may be useful laboratory evidence in selecting new no-opiod therapeutic medicine for morphine resistance and addiction.