Aim of the study: Parkinson’s disease (PD) is a neurodegenerative disorder. It is caused by the degeneration of dopaminergic neurons and the dopamine (DA) deletion in the substantia nigra pars compacta (SNpc). Morphine elevates the level of dopamine in the mesolimbic dopamine system and plays a role in alleviating PD symptoms. However, the molecular mechanism is still unclear. The aim of the study is to investigate the mechanism on morphine alleviating PD symptoms.
Materials and methods: The viability of PC12 cells was measured by using MTT assay. The expressions of tyrosine hydroxylase (TH), thioredoxin-1 (Trx-1), CyclinD1 and Cyclin-dependent kinase5 (Cdk5) were detected by Western Blot.
Results: In present study, we found that morphine increased the cell viability in PC12 cells. 1-methyl-4-phenylpyridi-nium (MPP+) reduced the cell viability and TH expression, which were reversed by morphine. MPP+ decreased the expressions of Trx-1, CyclinD1, Cdk5, which were restored by morphine. Moreover, the role of morphine in restoring the expressions of Trx-1, CyclinD1 and Cdk5 decreased by MPP+ was abolished by LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt inhibitor.
Conclusions: These results suggest that morphine reverses effects induced by MPP þ through activating PI3K/Akt pathway. 相似文献
Our previous work demonstrated that the hormone response to stress and the negative feedback inhibition to these hormones are sex-dependently altered by prenatal morphine exposure in adult rats. An alteration in the glucocorticoid negative feedback inhibition is mediated by glucocorticoid receptors (GR) that are distributed throughout the brain, and mineralocorticoid receptors (MR) localized mainly in the hippocampus and involved in a tonic influence of brain functions. Therefore, the present study examined the binding characteristics of MR and GR in young adult male and female rats exposed prenatally (E11-E18) to morphine (10 mg/kg/2 x /day), saline or no treatment at all (controls). At 60-90 days of age, animals were adrenalectomized (ADX) 24 h prior to decapitation. The hippocampus and hypothalamus were dissected for saturation binding assays. The data demonstrate that prenatal stress due to maternal saline injections up-regulates MR and GR binding in the hippocampus of adult male rats and this effect is prevented by prenatal morphine exposure. There is no effect of prenatal morphine exposure on GR binding in the hypothalamus of males. In female rats, prenatal morphine exposure does not affect the binding of MR and GR in the hippocampus or GR in the hypothalamus relative to controls; however, they are affected by ovarian hormone fluctuation. Moreover, prenatal stress decreases MR binding in the hippocampus of diestrous females and GR binding in the hypothalamus of estrous females. Both decreases are prevented by prenatal morphine exposure. Thus, the present study demonstrates that: (1) prenatal stress due to maternal saline injections alters MR and GR binding of adult male and female rats and is prevented by prenatal morphine exposure; (2) the MR and GR binding in adult female rats are affected by ovarian hormone fluctuations. 相似文献
BACKGROUND: Personality traits are associated with substance dependence (SD); genetic factors may influence both. Strong associations between ADH4 variation and SD have been reported. We aimed to investigate the relationship between ADH4 variation and personality traits in the present study. METHODS: We assessed dimensions of the five-factor model of personality in 243 subjects with SD (175 European Americans [EAs] and 68 African Americans [AAs]) and 296 healthy control subjects (256 EAs and 40 AAs). We also genotyped 7 ADH4 markers (spanning the locus) and 38 unlinked ancestry-informative markers in these subjects. The relationships between the diplotypes, alleles, and genotypes at ADH4 and personality traits were examined using multivariate analysis of covariance (MANCOVA), controlling for potential confounders. RESULTS: Generally, SD patients, older individuals, and male subjects scored higher on neuroticism and lower on other personality factors. Personality factors were associated with the diplotypes. The allele A or genotype A/A of single nucleotide polymorphism (SNP)6 (rs1800759 at the gene promoter) was significantly associated with agreeableness scores. There were associations between extraversion and SNP1 (hcv2033010 at the 3' end) and SNP2 (rs1042364 in exon 9) in subjects with higher conscientiousness scores. CONCLUSIONS: The personality traits of agreeableness and extraversion are related to ADH4 polymorphism. Among the ADH4 markers that appear to predispose to certain personality traits, the functional variant rs1800759 (SNP6) in the promoter region is most important. We conclude that personality traits and SD have a partially overlapping genetic basis. 相似文献
Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid
dependence. The purpose of this study was to determine the abuse liability of parenteral buprenorphine in volunteers maintained
on daily sublingual (SL) buprenorphine (8 mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges
two times per week. Medication challenges were 16 h after the daily dose of buprenorphine, and consisted of double-blind IM
injections of buprenorphine (4, 8, 16 mg), the prototypic mu opioid agonist hydromorphone (9 and 18 mg), or saline. Assessments
consisted of physiologic monitoring, subjects’ self-reports, and a trained observer’s ratings of drug effects, and were collected
for 0.5 h before and 2.0 h following injection. Supplemental doses of IM buprenorphine produced opioid agonist-like effects,
indicating some abuse potential of parenteral buprenorphine in buprenorphine-maintained patients. There was incomplete cross-tolerance
to the effects of hydromorphone, suggesting that higher maintenance doses of buprenorphine may be needed to maximize clinical
efficacy. However, there was a lack of graded dose-effects for hydromorphone, suggesting that buprenorphine’s combination
of partial agonist effects and high affinity for opioid receptors may limit the magnitude of effects of supplemental full
agonists. Finally, participants tolerated cumulative doses of maintenance buprenorphine plus challenge buprenorphine without
adverse effects, suggesting higher doses of buprenorphine can be safely administered to opioid dependent patients.
Received: 22 February 1996/Final version: 23 August 1996 相似文献
Summary A double-blind, placebo-controlled study has been made of the analgesic and respiratory effects of constant rate infusions
of meptazinol and morphine in 30 patients after abdominal surgery.
Group I received meptazinol, loading dose 50 mg followed by i.v. infusion 0.5 mg · kg−1 · h−1, Group II received morphine, loading dose 5 mg and then an infusion of 0.05 mg · kg−1 · h−1, and Group III received saline.
After recovery from inhalation anaesthesia (without opiates or a local anaesthetic) pain relief and chemoreceptor carbon dioxide
tolerance were assessed before and at various times after starting the analgesic infusion. A similar degree of pain relief
was found after 10 min in Groups I and II, which lasted until the end of observation period (20 h). Heart rate and systolic
and diastolic blood pressures were lower in Group II than in Groups I and III, and respiratory rate fell in Groups I and II.
After 6 h arterial carbon dioxide tensions (PaCO2) became significantly higher in Group II than Group III. The maximum percentage fall in mean tidal volume (VT) and expired minute volume (0VE) from the preinjection values was significant in Groups I and II. End-tidal carbon-dioxide (PETCO2) and PaCO2 were significantly higher after 20 h of infusion in Group II compared to Group I. The slope of 0VE/PETCO2 (<S>) was increased in Group I and it was significantly reduced in Group II. Analysis of derived variables, such as the CO2 intercept (CO2I) and minute ventilation at 7 kPa (0VE7), indicated a shift to the right of the slopes in Groups I and II, initially more so in Group I.
It is concluded that constant rate infusions of meptazinol and morphine were effective in providing postoperative pain relief.
However, their effects on the central regulation of respiration were different, as meptazinol did not impair CO2 sensitivity whereas morphine did. 相似文献