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1.
This study was performed to evaluate the effects of dynorphin A(1–13) antiserum when microinjected into an active hyperalgesic region within the rat brain stem. When administered within the dorsal posterior mesencephalic tegmentum (DPMT) of intact conscious rats, dynorphin A(1–13) antiserum produced rapid onset and persistent prolongation of a low intensity thermally evoked tail avoidance response (LITETAR). These analgesic actions of the dynorphin A(1–13) antiserum appeared to be dose dependent. These studies support previous hypotheses about the existence of tonically active brain stem opioid hyperalgesic processes. Further, the results provide indirect evidence for a potential role of brain stem dynorphin(s) in facilitating pain. 相似文献
2.
B. Griffond S. Grillon J. Duval C. Colard C. Jacquemard A. Deray D. Fellmann 《Journal of chemical neuroanatomy》1995,9(2):113-119
The occurrence of secretogranin II in a neuron population of the rat lateral hypothalamus specifically detected by an anti-serum to ovine prolactin was examined. As this population was previously reported to synthesize dynorphin, the distribution of neurons recognized by ovine prolactin-, dynorphin B- and secretogranin II anti-sera was investigated on adjacent sections of hypothalami. The prolactin immunoreactive neurons were the only cells in the lateral hypothalamus to be stained by secretogranin II anti-serum. Moreover, coupling immunocytochemical detection and in situ hybridization with an oligonucleotide probe complementary to secretogranin II mRNA showed that these neurons expressed the secretogranin II gene. These new findings should help to study the physiological role of the prolactin immunoreactive neurons of the lateral hypothalamus. 相似文献
3.
Gonzalo Herradon Laura Ezquerra Trang Nguyen Chi Wang Ana Siso Barbara Franklin Laura Dilorenzo Julie Rossenfeld Inmaculada Silos-Santiago Luis F. Alguacil 《Neuroscience letters》2008
The Fischer 344 (F344) rat strain differs from the Lewis strain in the response to neuropathic pain. Recently, we found that F344 rats totally recover from mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve 28 days after surgery whereas Lewis rats are initiating their recovery at this time point. Thus, the use of this neuropathic pain model in these different rat strains constitutes a good strategy to identify possible target genes involved in the development of neuropathic pain. Since differences between Lewis and F344 rats in their response to pain stimuli in acute pain models have been related to differences in the endogenous opioid and noradrenergic systems, we aimed to determine the levels of expression of key genes of both systems in the spinal cord and dorsal root ganglia (DRG) of both strains 28 days after CCI surgery. Real time RT-PCR revealed minimal changes in gene expression in the spinal cord after CCI despite the strain considered, but marked changes in DRG were observed. A significant upregulation of prodynorphin gene expression occurred only in injured DRG of F344 rats, the most resistant strain to neuropathic pain. In addition, we found a significant downregulation of tyrosine hydroxylase and proenkephalin gene expression levels in both strains whereas δ-opioid receptor was found to be significantly downregulated only in injured DRG of Lewis rats although the same trend was observed in F344 rats. The data strongly suggest that dynorphins could be involved in strain differences concerning CCI resistance. 相似文献
4.
M. S. Reid M. Herrera-Marschitz T. Hökfelt N. Lindefors H. Persson U. Ungerstedt 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1990,82(2):293-303
Summary The striatonigral pathway contains several neurotransmitters which may regulate the activity of the nigrostriatal dopamine projection in the rat. This was investigated by measuring extracellular dopamine levels in the striatum, using microdialysis, after injections of GABA (300 nmol/0.2 l), dynorphin A (0.5 nmol/0.2 l), substance P (0.07 mnol/0.2 l) or neurokinin A (0.09 nmol/0.2 l) into the ipsilateral substantia nigra, pars reticulata (SNR). Intranigral injections of GABA or dynorphin A inhibited, while intranigral injections of substance P or neurokinin A stimulated dopamine levels in the ipsilateral striatum. In rats with ibotenic acid lesions (2.5 g/0.5 l) in the SNR, intranigral injections of GABA or dynorphin A inhibited, while intranigral injections of substance P or neurokinin A stimulated dopamine levels in the ipsilateral striatum. These responses were not significantly different than those in unlesioned rats. Analysis of the intranigral lesion with in situ hybridization revealed a heavy loss of glutamic acid decarboxylase mRNA expression in the SNR and a significant loss of tyrosine hydroxylase (TH) mRNA expression in the SNC. Immunohistochemical analysis revealed a disappearance of TH-Like immunoreactivity (LI) im dendrites in the SNR, a considerable loss of TH-LI cell bodies in the SNC and a restricted loss of neuropeptide K-LI in the SNR around the tip of the injection cannula. Furthermore, lesioned rats rotated ipsilateral to the lesion after apomorphine (1 mg/kg, s.c.), indicating that the basal ganglia output mediated via the SNR GABA neurons was impaired on the lesioned side. Analysis of the striatum revealed that a dense TH-LI fiber network could still be seen on the lesioned side. Furthermore, basal and amphetamine stimulated extracellular dopamine levels in the striatum on the lesioned side were not significantly depleted. This indicates that the ascending nigrostriatal dopamine projection was functionally intact on the lesioned side. These findings indicate that intranigral GABA, dynorphin A, substance P and neurokinin A modulation of ipsilateral striatal dopamine release is mediated via direct action on the nigrostriatal projection. Thus, it is suggested that the striatonigral pathway, which contains GABA, dynorphin, substance P and neurokinin A, exerts a direct regulatory effect on the activity of the nigrostriatal dopamine projection. 相似文献
5.
Cisplatin-induced long-term dynorphin A-immunoreactivity in cell somata of rat area postrema neurons
Goichi Tsukamoto Hiroyuki Ichikawa Motoi Kobashi Yosuke Yamada Takeshi Kikuchi Hiroshi Mese Akira Sasaki 《Neuroscience letters》2007
We evaluated long-term dynorphin A-immunoreactivity in the rat area postrema (AP) after the administration of cisplatin. First, rats were given 1, 5 and 10 mg/kg body weight cisplatin (i.p.) and their behavior was monitored for 72 h. We observed a delayed increase in pica 24-72 h after injection, compared to the 24 h before injection. We attributed this to the cisplatin injection. Pica was defined as an increase in the intake of non-nutritional matter such as kaolin. Administration of 1, 5 and 10 mg/kg cisplatin led to an increase in kaolin intake on day 1. Administration of 5 and 10 mg/kg of cisplatin led to decreased intake of laboratory chow (MF) on days 1–3, but 10 mg/kg cisplatin causes an excessive aggravation of their condition. Following this behavioral experiment, we immunohistochemically examined the induction of dynorphin A in the AP at 24, 48 and 72 h post-administration of 1 and 5 mg/kg cisplatin. Administration of 5 mg/kg cisplatin caused dynorphin A to accumulate gradually in the neurosoma of the AP neurons, and the numbers of positive AP neurosomata at 48 and 72 h post-administration were higher than following an equal dosage of 0.9% NaCl. These findings suggest that dynorphin A increases in the central nervous system for a long time following administration, and causes certain behavioral and clinical changes, including those related to appetite and nausea. 相似文献
6.
M B Essatara J E Morley A S Levine M K Elson R B Shafer C J McClain 《Physiology & behavior》1984,32(3):475-478
Anorexia is a major symptom of zinc deficiency, but the mechanism(s) for this anorexia are poorly defined. Recent studies have suggested an integral role for endogenous opiate peptides in appetite regulation. Dynorphin, a leucine-enkephalin containing opiate peptide, is a potent inducer of spontaneous feeding. In this study we showed that zinc deficient animals were relatively resistant to dynorphin-induced feeding. Measurement of dynorphin levels using a highly sensitive radioimmunoassay showed that zinc deficient animals had lower levels of dynorphin in the hypothalamus than did ad lib fed animals, with weight restricted animals having intermediate values. [3H]-naloxone binding was significantly increased to isolated brain membranes from zinc deficient animals using 1 nM unlabeled naloxone when compared to ad lib fed controls with the weight restricted animals again having intermediate values. These data suggest that abnormalities in endogenous opiate regulation of appetite may well play a role in the anorexia of zinc deficiency. The effects of zinc deficiency on endogenous opiate action appear to include alterations in receptor affinity, a post-receptor defect and alterations in the synthesis and/or release of dynorphin. 相似文献
7.
Dynorphin has a well-established role in feeding and gustation. Alterations in taste perception and feeding behavior are common with age. We hypothesized that proDynorphin gene expression in brain areas involved in taste and feeding declines with age. Male Sprague-Dawley rats were housed individually with ad libitum access to food and water. Brain punches of the selected regions were dissected out in groups of rats aged 4–6, 12–14 and 18–21 months. ProDynorphin mRNA (measured using a cDNA probe) decreased significantly with age in arcuate nucleus and amygdala; increased significantly with age in hippocampus; and was not significantly affected in nucleus of the solitary tract, cortex, caudate putamen or hypothalamic paraventricular nucleus. These data suggest an age-related decrease in the synthesis of dynorphin in two brain regions strongly associated with feeding behavior, and an increase in dynorphin synthesis in a brain region associated with learning and memory. 相似文献
8.
Gary T. Shearman Rüdiger Schulz Peter W. Schiller Albert Herz 《Psychopharmacology》1985,85(4):440-443
Rats were trained in a two-lever food-reinforced procedure to discriminate between the effects of saline and the opioid kappa receptor agonist ethylketocyclazocine. After acquisition of this discrimination, generalization tests with opioid peptides such as -endorphin, -neoendorphin, dynorphin A and some dynorphin-derived peptides were conducted. The rats dose-dependently generalized the effects of intracerebroventricularly injected ethylketocyclazocine but not -endorphin, -neoendorphin, dynorphin A1–8, dynorphin A1–13, D-Cys2-L-Cys5-dynorphin A1–13 or dynorphin A.
D-Cys2-L-Cys5-dynorphin A1–13, in contrast to dynorphin A itself, dose-dependently caused analgesia and catatonia that was reversible with naloxone. Studies into the receptor preference of this derivative, using the technique of selective tolerance, revealed that this dynorphin derivative is almost devoid of kappa-receptor activity. 相似文献
9.
In binding assays, both dynorphin B and alpha-neoendorphin are relatively selective for the kappa1b site, unlike U50,488H which has high affinity for both kappa1a and kappa1b sites. In vivo, U50,488H, dynorphin B and alpha-neoendorphin analgesia are reversed by the kappa1-selective antagonist, nor-binaltorphimine (norBNI). Antisense mapping the three exons of KOR-1 revealed that probes targeting all three exons blocked U50,488H analgesia, as expected. However, the selectivity profile of dynorphin B and alpha-neoendorphin analgesia towards the various antisense oligodeoxynucleotides differed markedly from U50,488H, implying a different receptor mechanism of action. 相似文献
10.
目的 探讨前强啡肽(PDP)基因修饰的人骨髓间充质干细胞株(hBMSCs-PDP)对神经病理性疼痛模型大鼠的镇痛效应.方法 将雄性SD大鼠随机分为4组(n-10):A组为正常对照组,B、C、D组制备CCI模型.术后3d将hBMSCs-PDP移植入CCI模型大鼠髓鞘内,A组不做处理;B组鞘内注射生理盐水20 μl;C组鞘内注射hBMSCs-空载体悬液20 μl(约106/μl);D组鞘内注射hBMSCs-PDP悬液20 μl(约106/μl).分别于术前、术后3、5、7、9、11、13d测定大鼠足底的热痛阈值.术后13d取脊髓组织,用免疫组织化学法和Western Blot法测定脊髓强啡肽表达情况.结果 与A组比较,B、C及D组大鼠热痛阈降低;与B、C组相比,D组大鼠脊髓组织强啡肽表达增强,Western Blot法证实其强啡肽蛋白的分泌增加.注入hBMSCs-PDP细胞CCI模型大鼠的热痛阈值也比其它两组有所升高,差异有统计学意义(P<0.05).结论 鞘内注射hBMSCs-PDP可提高脊髓组织强啡肽的表达,对CCI模型大鼠起到一定镇痛作用. 相似文献