1.Inhibition of the reinstatement of morphine-induced place preference in rats by high-frequency stimulation of the bilateral nucleus accumbens.
Yu MA ; Ning CHEN ; Hui-Min WANG ; Fan-Gang MENG ; Jian-Guo ZHANG
Chinese Medical Journal 2013;126(10):1939-1943
BACKGROUNDOpiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery. Many studies have identified a central role of the nucleus accumbens (NAc) in addiction. Deep brain stimulation (DBS) has the advantages of being reversible, adjustable, and minimally invasive, and it has become a potential neurobiological intervention for addiction. The purpose of our study was to investigate whether high-frequency DBS in the NAc effectively attenuates the reinstatement of morphine seeking in morphine-primed rats.
METHODSA morphine-dependent group of rats was given increasing doses of morphine during conditioned place preference training. A control group of rats was given equal volumes of saline. After the establishment of this model, withdrawal syndromes were precipitated in these two groups by administering naloxone, and the differences in withdrawal symptoms between the groups were analyzed. Electrodes for DBS were implanted in the bilateral shell of the NAc in the experimental group. The rats were stimulated daily in the NAc for 5 hours per day over 30 days. Changes in the conditioned place preference test and withdrawal symptoms in the rats were investigated and place navigation studies were performed using the Morris water maze. The data were assessed statistically with one-way analysis of variance (ANOVA) followed by Tukey's tests for multiple post hoc comparisons.
RESULTSHigh-frequency stimulation of the bilateral NAc prevented the morphine-induced reinstatement of morphine seeking in the conditioned place preference test. The time spent in the white compartment by rats following 30 days of DBS ((268.25 ± 25.07) seconds) was not significantly different compared with the time spent in the white compartment after relapse was induced by morphine administration ((303.29 ± 34.22) seconds). High-frequency stimulation of the bilateral NAc accelerated the innate decay of drug craving in morphine-dependent rats without significantly influencing learning and memory.
CONCLUSIONBilateral high-frequency stimulation of the shell of the NAc may be useful as a novel therapeutic modality for the treatment of severe morphine addiction.
Animals ; Electric Stimulation ; Male ; Morphine ; toxicity ; Morphine Dependence ; therapy ; Nucleus Accumbens ; metabolism ; Rats ; Rats, Sprague-Dawley
2.Effects of scopolamine on morphine-dependence in mice and the relationship between the effect and hippocampus intracellular calcium.
Li-guang WANG ; Xin-hua GUO ; Ling-Yun LIU ; Bai-ying PENG ; Yu-ning LIU ; Jun-hong QIAO
Chinese Journal of Applied Physiology 2006;22(3):307-309
AIMTo observe the effect and mechanism of scopolamine on morphine(Mor)-induced mice dependence.
METHODSThe Mor-dependent mice model was established by intraperitoneal (ip) administered Mor for seven days. Pain threshold, times of jump and hippocampus intracellular free calcium ion concentration ([Ca2+]i) were determined by the heat plate test, naloxone (Nal)-precipitated jumping response and flow cytometry, respectively.
RESULTSThe pain threshold of Mor-dependent mice decreased significantly while there was a marked increase in times of jump, the rate of jumping animals and hippocampus [Ca2+]i. Co-administered scopolamine, the pain threshold of Mor-dependent mice increased significantly; the number of jump, the rate of jumping animals and hippocampus [Ca2+]i all decreased significantly.
CONCLUSIONScopolamine could antagonize the Mor-induced mice dependence, which could be related to decreasing the levels of brain intracellular free calcium.
Animals ; Calcium ; metabolism ; Hippocampus ; cytology ; drug effects ; metabolism ; Mice ; Mice, Inbred Strains ; Morphine ; pharmacology ; Morphine Dependence ; metabolism ; Scopolamine Hydrobromide ; pharmacology
3.An immunohistochemical study on the distribution in organs in cases with morphine poisoning.
Ya-ming SHAN ; Chun-yu HAO ; Long WANG
Journal of Forensic Medicine 2002;18(1):9-11
OBJECTIVE:
To investigate the distribution of mophine in organs in cases with morphine poisioning to select ideal organs for immunohistochemical derection.
METHODS:
Localization and half quantitation of morphine in the brain, the kidney, the heart, and the liver were studied in 8 cases with morphine poisoning by immunohistochemical SP method.
RESULTS:
Morphine was mainly detected in the cytoplasm of certain parenchymal cells of the organs. The distribution varied greatly with different cases and organs. In the brain and kidney, morphine-positive cells could be easily found.
CONCLUSION
The kidney and brain may be the ideal organs for sampling in suspected morphine poisoning cases with.
Adult
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Brain/metabolism*
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Female
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Forensic Medicine
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Humans
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Immunohistochemistry
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Kidney/metabolism*
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Male
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Morphine/poisoning*
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Morphine Dependence/metabolism*
;
Tissue Distribution
6.The research of the heroin and its metabolites analysis in clinical samples.
Lan LIN ; Lin-chuan LIAO ; You-yi YAN
Journal of Forensic Medicine 2003;19(2):126-128
Heroin can be metabolized easily in body and the mail metabolites are 6-MAM, morphine and so on. At present, there are urine, blood, hair and so on as specimens for detection, while the analytical technology conclude TLC, GC, HPLC, GC/MS, LC/MS, IA, CE etc. In this paper, these technologies used for heroin's metabolites were viewed in order to provide some reference to the study in relative field.
Chromatography, High Pressure Liquid
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Forensic Medicine
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Gas Chromatography-Mass Spectrometry
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Hair/chemistry*
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Heroin/metabolism*
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Heroin Dependence/metabolism*
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Humans
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Morphine/analysis*
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Morphine Derivatives/analysis*
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Substance Abuse Detection/methods*
7.Effects of ginsenosides on the actions of morphine.
Ming GUO ; Chun-fu WU ; Jin-hui WANG ; Gang PEI
China Journal of Chinese Materia Medica 2004;29(4):299-301
The effects of ginsenosides on the actions of morphine are summarized. It mainly focuses on the antagonistic effects of ginsenosides on morphine-induced changes of animal behaviors, neural system functions and cell signaling transduction.
Animals
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Behavior, Animal
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drug effects
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Body Weight
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drug effects
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Ginsenosides
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pharmacology
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Mice
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Morphine
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antagonists & inhibitors
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pharmacology
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Morphine Dependence
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Neurotransmitter Agents
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metabolism
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Rats
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Signal Transduction
;
drug effects
8.The development of research on enzymes related to morphine-dependent.
Journal of Forensic Medicine 2005;21(2):152-158
The mechanism of morphine dependent is a complex Procedure. It involves in many complex mechanisms such as the ultra-structure of synapse of special brain areas, neurotransmitter, enzymology, and so on. These mechanisms have closely correlation. In this paper we reveiwed the development in enzymological mechanism of morphine dependent enzymes including protein kinase (PK), nitric oxide synthase (NOS), superoxide dismutase (SOD), adenylate cyclase (AC), Succinate dehydrogenase (SDH)and 3beta-Hydroxy steroid dehydrogenase (3beta-HSD).
Adenylyl Cyclases/metabolism*
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Animals
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Brain/enzymology*
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Morphine Dependence/pathology*
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Nitric Oxide Synthase/metabolism*
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Protein Kinases/metabolism*
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Substance Withdrawal Syndrome/metabolism*
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Succinate Dehydrogenase/metabolism*
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Superoxide Dismutase/metabolism*
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Synapses/enzymology*
9.The role of the spinal cord inducible nitric oxide synthase in morphine dependence and naloxone-precipitated withdrawal rats.
Hai-Lin LIU ; Yan-Ning QIAN ; Xiang-Cheng LI
Chinese Journal of Applied Physiology 2012;28(1):49-52
OBJECTIVETo explore if induced nitric oxide in the spinal cord mediates withdrawal syndrome in morphine-dependent rats.
METHODSMale SD rats weighing 200-250 g were employed in the present study. To set up morphine dependence model, rats were subcutaneously injected with morphine (twice a day, for 5 d). The dose of morphine was 10 mg/kg in the first day and was increased by 10 mg/kg each day. On day 6, 4 h after the injection of morphine (50 mg/kg), morphine withdrawal syndrome was precipitated by an injection of naloxone (4 mg/kg, ip). Inducible nitric oxide synthase (iNOS) inhibitors aminoguanidine (AG) was intrathecally injected 30 min before the administration of naloxone. All the rats were divided into four groups: control group, dependence group, withdrawal group, AG group. Morphine withdrawal score, touch evoked agitation scores (TEA scores), immunohistochemical and Western blot technique were used to evaluate morphine withdrawal response and the expression of iNOS in the spinal cord.
RESULTSIntrathecal injection of iNOS inhibitors AG could alleviate morphine withdrawal symptoms. Morphine withdrawal scores and touch evoked agitation scores in AG group were significantly lower than that of withdrawal group (P < 0.05). iNOS positive neurons in dorsal horn of AG group were significantly lower than that of withdrawal group (P < 0.05). Level of iNOS protein in spinal cord of AG group was significantly lower than that of withdrawal group (P < 0.05).
CONCLUSIONInduced nitric oxide in the spinal cord may mediate withdrawal syndrome in morphine-dependent rats.
Animals ; Male ; Morphine Dependence ; metabolism ; Naloxone ; pharmacology ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; metabolism ; Substance Withdrawal Syndrome ; metabolism
10.Melatonin enhances the expression of β-endorphin in hypothalamic arcuate nucleus of morphine-dependent mice.
Yi-Ming WEI ; Ying XU ; Chang-Xi YU ; Jing HAN
Acta Physiologica Sinica 2009;61(3):255-262
The study was conducted to investigate the effect of melatonin (MEL) on the expression of β-endorphin (β-EP) in the hypothalamic arcuate nucleus (ARH) of morphine-dependent mice. For a period of 8 consecutive days, male Kunming strain mice were injected subcutaneously (s.c.) with normal saline or increasing doses (10-80 mg/kg) of morphine, and intraperitoneally (i.p.) with MEL (10, 20 or 40 mg/kg) or vehicle (5% ethanol saline) simultaneously. Withdrawal response was induced by naloxone (3 mg/kg, s.c.) at 2 h after final morphine injection on the 8th day. The potency of withdrawal response was evaluated according to the jumping times and the body weight loss. After that, the expressions of β-EP and proopiomelanocortin (POMC) mRNA in ARH were examined by immunohistochemistry and RT-PCR, respectively. The results showed that MEL (i.p., 20 mg/kg) decreased the naloxone-precipitated withdrawal responses in morphine-dependent mice significantly (P<0.05). Meanwhile, MEL increased the intensity of β-EP-like immunoreactivity and enhanced the expression of POMC mRNA in ARH (P<0.05). These results suggest that MEL increases the expression of β-EP in ARH of morphine-dependent mice, which may partly contribute to the action of MEL to inhibit the development of morphine dependence.
Animals
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Arcuate Nucleus of Hypothalamus
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drug effects
;
metabolism
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Male
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Melatonin
;
pharmacology
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Mice
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Morphine
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pharmacology
;
Morphine Dependence
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metabolism
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Naloxone
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pharmacology
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Pro-Opiomelanocortin
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metabolism
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RNA, Messenger
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metabolism
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Substance Withdrawal Syndrome
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metabolism
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beta-Endorphin
;
metabolism