sinomenine and Morphine-Dependence

Evidence suggests that the dopamine receptor rate-limiting enzyme, tyrosine hydroxylase (TH), and the glutamate receptor, N-methyl-D-aspartate receptor 2B (NR2B), contribute to morphine dependence. Previous studies show that chronic exposure to morphine changes the expression of opioid receptors. In this study, we focus on the effects of sinomenine on morphine-dependent mice and its related neural mechanisms. Conditioned place preference (CPP) mouse model was established using morphine (9 mg/kg, s.c.), and their expression levels of TH and NR2B were observed by immunohistochemistry. Moreover, their mu opioid receptor (MOR) and delta opioid receptor (DOR) contents were assessed using quantitative reverse transcription polymerase chain reaction. Results showed that high sinomenine dose (80 mg/kg) effectively attenuated the behavior of CPP mice and reversed increased expression levels of TH and NR2B induced by morphine. Moreover, compared with the morphine group, sinomenine up-regulated the content of MOR to a normal level but did not significantly affect the DOR expression. In summary, these data indicate that sinomenine can inhibit morphine dependence by increasing the expression levels of TH, NR2B, and MOR in the mouse brain; however, DOR may not contribute to this effect.

Topics: Animals; Brain; Mice; Morphinans; Morphine; Morphine Dependence; Neurons; Receptors, N-Methyl-D-Aspartate; Receptors, Opioid; Tyrosine 3-Monooxygenase

To observe the effect of alcohol extracts from orientivne and its effective component sinomenine on withdrawal syndromes and neurotransmitter of morphine-abstinent mice and on intracellular calcium level in morphine-dependent neuronal-cells line. To study the detoxification of alcohol extracts from orientvine and sinomenine on morphine-dependent animal and explore the mechanism of its effect.. The effect of alcohol extracts from orientivne and sinomenineon on abstinent syndromes was observed by experiment study on morphine-dependent ex vivo ileum from guinea pigs and morphine-dependent mice. The morphine-dependent model mice were established by injection on dosage increasing by degrees. The hypothalamic monomine neurotransmitters such as NA, DA, 5-HT were tested by fluorospectrophotometry. Morphine-dependent cell line was established by administering morphine at different doses into the culture medium. The cells were stained with fluo-3 and the intracellular calcium level was measured by flow cytometry.. Alcohol extracts from orientvine and sinomenine could alleviate withdrawal contractile response of morphine-dependent ex vivo ileum from guinea pigs and withdrawal syndromes of morphine-dependent mice, decrease the concentration of the neurotransmitters, and elevate the intracellular calcium level and inhibit the decreasing of Ca2+ induced by naloxone.. Alcohol extracts from orientvine and sinomenine have some effects on withdrawal syndromes which may be related to inhibiting neurotransmitters and the regulation of intracellular calcium concentration.

Topics: Animals; Calcium; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Ethanol; Female; Guinea Pigs; Ileum; Male; Mice; Morphinans; Morphine; Morphine Dependence; Muscle Contraction; Neurons; Norepinephrine; Random Allocation; Rats; Rats, Sprague-Dawley; Sinomenium; Substance Withdrawal Syndrome

Topics: Animals; Brain; Male; Mice; Mice, Inbred Strains; Morphinans; Morphine Dependence; Nitric Oxide Synthase Type I

To evaluate the effects of Caulis Sinomenii and sinomenine on conditioned place preference (CPP) induced by morphine and brain histamine level in mice.. Sixty mice were randomized into 6 equal groups and morphine (Mor) was injected subcutaneously (9 mg/kg) for 6 consecutive days to induce CPP using a shuttle box. Since the 4th day of training, the mice in 5 of the groups were treated for 3 consecutive days with Caulis Sinomenii (10 g/kg), sinomenine (60 mg/kg), diphenhydramine (30 mg/kg), CP48/80 (5 mg/kg) and L-histidine (750 mg/kg) in addition to morphine (9 mg/kg) treatment, respectively, leaving the other group with exclusive morphine treatment. Another 10 mice received saline injection to serve as saline control group. The content of histamine (HA) in the mouse brain was measured by fluorospectrophotometry.. In morphine group, the mice showed significantly extended stay in morphine-paired compartment whose HA content in the brain was markedly increased (P<0.01). Treatment with Caulis Sinomenii and sinomenine resulted in significantly reduced time of stay in morphine-paired compartment and brain HA level (P<0.01).. CPP induced by morphine in mice is associated with increased HA level in the brain. Caulis Sinomenii and sinomenine can suppress the acquisition of place preference induced by morphine and modulate HA level in the central nervous system in morphine-dependent mice.

Topics: Animals; Arginine; Brain; Conditioning, Operant; Diphenhydramine; Histamine; Male; Mice; Morphinans; Morphine; Morphine Dependence; Motor Activity; Random Allocation; Sinomenium

To explore the effects of long-term morphine exposure on cAMP and cGMP levels in primary cultured tuberomammillary nucleus (TM) neurons of neonatal rats and the effects of sinomenine on morphine-dependent TM cells.. TM neurons after a 7-day primary culture were further cultured in the medium containing 100 micromol/L morphine for 48 h to prepare the cell model of morphine dependence. Serial doses of histamine or sinomenine were administered 30 min naloxone treatment, the cAMP and cGMP levels of the TM cells were determined by enzyme immunoassay. cAMP and cGMP levels were also determined in normal TM cells treated by histamine or sinomenine.. After treatment with 100 micromol/L morphine for 48 h, cAMP and cGMP levels in the TM neurons were increased markedly. Treatment with 100 micromol/L naloxone added in the culture media caused an overshoot of cellular cAMP and a marked declination of cGMP, resulting in significantly increased cAMP/cGMP ratio. Sinomenine at 30 and 100 micromol/L and histamine at 40 micromol/L failed to obviously affect cAMP and cGMP levels in normal TM neurons, but sinomenine at 300 micromol/L and histamine at 80 micromol/L significantly increased the intracellular cAMP level. After pre-treatment with sinomenine at the above 3 doses or histamine at 40 micromol/L, the TM neurons with morphine dependence exhibited significant reduction in intracellular cAMP level but increment in cGMP level after naloxone treatment, with significantly reduced cAMP/cGMP ratio.. Long-term morphine (100 micromol/L) exposure for 48 h can induce marked changes of cAMP and cGMP levels in the TM neurons. The central histaminergic nervous system may be responsible for the development of morphine dependence and withdrawal. Sinomenine can significantly reduce the cAMP level and enhance cGMP level of morphine-dependent TM neurons precipitated by naloxone, which results in a near-normal ratio of cAMP and cGMP.

Topics: Animals; Animals, Newborn; Cells, Cultured; Cyclic AMP; Cyclic GMP; Female; Histamine; Hypothalamus; Morphinans; Morphine; Morphine Dependence; Neurons; Rats; Rats, Sprague-Dawley

To investigate the effects of sinomenine on morphine withdrawal response and acetylchline (Ach)-induced contracture in isolated guinea pig ileum.. The withdrawal contracture was elicited by subjecting isolated ileum incubated with morphine (3 micromol/L) at 37.5 degrees Celsius for 4 h to naloxone (1 micromol/L) treatment. Sinomenine (10, 50, 250 micromol/L) and nimodipine (Nim, 0.1 micromol/L) were administered 1 min before and after naloxone in morphine-dependent ilea bathed in Krebs solution containing morphine, to observe the changes in the withdrawal contracture of the ileum. The effect of sinomenine (10, 50, 250 micromol/L) on the contracture of untreated ileum in Krebs solution elicited by acetylcholine was also observed.. Naloxone-induced withdrawal contracture or acetylcholine-induced contracture of the ileum was significantly decreased in a dose-dependent manner, indicating that sinomenine can inhibit morphine withdrawal symptoms in guinea pigs.

Topics: Animals; Guinea Pigs; Ileum; Morphinans; Morphine; Morphine Dependence; Muscle Contraction; Naloxone; Nimodipine; Substance Withdrawal Syndrome

To study on the detoxification effect of sinamine in morphine-dependent rats.. Morphine-dependent rats were induced by injecting morphine on dosage increasing by degrees, then treated with medication. The withdrawal symptoms, body weight and NE, DA, 5-HT in the brain were tested.. Sinamine could alleviate withdrawal symptom, reablement body weight, inhibit neurotransmitter in the brain.. Sinamine have effects on morphine-dependent rats which may relate to modulating neurotransmitter.

Topics: Animals; Biogenic Monoamines; Body Weight; Brain; Dopamine; Male; Morphinans; Morphine Dependence; Norepinephrine; Rats; Serotonin; Substance Withdrawal Syndrome