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Sensitization to psychostimulant drugs, as well as morphine, subjected to cross-sensitization with stress. The development of morphine sensitization is associated with enhancements in dopamine overflow in the Nucleus accumbens (NAc). This study aimed to examine the role of accumbal D1/D2-like dopamine receptors in restraint stress (RS) induced sensitization to morphine antinociceptive effects. Adult male Wistar rats weighing 220–250 g underwent stereotaxic surgery. Two stainless steel guide cannulae were bilaterally implanted, 1 mm above the NAc injection site. Different solutions of SCH-23390, as a D1-like receptor antagonist or sulpiride, as a D2-like receptor antagonist, were microinjected into the NAc five min before exposure to RS. Restraint stress lasted for 3 h, 10 min after RS termination; animals received a subcutaneous injection of morphine (1 mg/kg) for 3 consecutive days. The procedure was followed by a 5-day drug and/or stress-free period. After that, on the 9th day, the nociceptive response was evaluated by the tail-flick test. The results revealed that intra-NAc administration of D1/D2-like dopamine receptor antagonists, SCH-23390 or sulpiride, respectively, blocked morphine sensitization-induced by RS and morphine co-administration in rats for three consecutive days. This work provides new insight into the determinant role of accumbal dopamine receptors in morphine sensitization produced by RS-morphine co-administration.

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Small and silvery cyprinid species from eastern Iran which are usually known as Crossocheilus latius are reviewed based on morphological and molecular characters of the mtDNA COI barcode region. We demonstrate that fishes which had been identified as Crossocheilus Kuhl & van Hasselt, 1823 in Iran actually belong to the genus Gonorhynchus McClelland, 1838 with two species: G. adiscus (Annandale, 1919) and G. diplochilus (Heckel, 1838), which are rediagnosed here. Both species are well distinguished by gill raker counts, number of scales between anus and anal fin, barbel size and minimum body depth. G. adiscus and G. diplochilus are also distinguished by molecular characters of the mtDNA COI barcode region. Both species are phylogenetically close to Gonorhynchus latius (Hamilton, 1822) which is restricted to India, Nepal and Bangladesh and to G. burmanicus (Hora, 1936), restricted to India and Myanmar. All of these four related taxa are phylogenetically closer to the genus Garra than the genus Crossocheilus (restricted to south-east Asia).  相似文献   
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The crested loaches of the genus Paracobitis from the Sistan basin (Iran) are reviewed based on morphological and mitochondrial cytb and COI sequences characters to check the status of taxa in phylogenetic trees. Paracobitis rhadinaea (Regan, 1906) and P. vignai Nalbant & Bianco, 1998 were known only based on minor morphological differences (presence or absence of scales, caudal fin shape, colour pattern and fish size). We failed to find any diagnostic molecular and morphological characters between them. Therefore, we regard P. vignai as a junior synonym of P. rhadinaea.  相似文献   
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The primary aim of our meta-analysis was to evaluate the effects of cathodal transcranial direct current stimulation (c-tDCS) on sensory and pain thresholds (STh and PTh) in healthy individuals and pain level (PL) in patients with chronic pain. Electronic databases were searched for c-tDCS studies. Methodological quality was evaluated using the PEDro and Downs and Black (D&B) assessment tools. C-tDCS of the primary motor cortex (S1) increases both STh (P<0.001, effect size of 26.84%) and PTh (P<0.001, effect size of 11.62%). In addition, c-tDCS over M1 led to STh increase (P<0.005, effect size of 30.44%). Likewise, PL decreased significantly in the patient group following application of c-tDCS. The small number of studies precluded subgroup analysis. Nevertheless, meta-analysis showed that in all groups (except c-tDCS of S1) active c-tDCS and sham stimulation produced significant differences in STh/PTh in healthy and PL in patient group. This review provides evidence for the site-specific effectiveness of c-tDCS in increasing STh/PTh in healthy individuals and decreasing PL in patients with chronic pain. However, due to small sample sizes in the included studies, our results should be interpreted with caution. Given that the level of blinding was not considered in the inclusion criteria, the results of the current study should be interpreted with caution.  相似文献   
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Background

Neutralization of vascular endothelial growth factor receptor 1 (VEGFR1) and/or VEGFR2 is a widely used means of inhibiting tumor angiogenesis.

Methods

Based on the complex X-ray structures of VEGFA/VEGFR1, VEGFA/VEGFR2, and VEGFB/VEGFR1, a peptide (referred to as VGB) was designed to simultaneously bind to VEGFR1 and VEGFR2, and binding, antiangiogenic and antitumor properties of the peptide was investigated in vitro.

Results

VGB bound to both VEGFR1 and VEGFR2 in human umbilical vein endothelial cells (HUVECs) and 4?T1 mammary carcinoma tumor (MCT) cells, and inhibited the proliferation of HUVE, 4?T1 MCT, and U87 glioblastoma cells. Through abrogation of AKT and ERK1/2 phosphorylation, VEGFA-stimulated proliferation, migration, and two- and three-dimensional tube formation in HUVECs were inhibited more potently by VGB than by bevacizumab. In a murine 4?T1 MCT model, VGB strongly inhibited tumor growth without causing weight loss, accompanied by inhibition of AKT and ERK1/2 phosphorylation, a significant decrease in tumor cell proliferation (Ki-67 expression), angiogenesis (CD31 and CD34 expression), an increase in apoptosis index (increased TUNEL staining and p53 expression and decreased Bcl-2 expression), and the suppression of systematic spreading of the tumor (reduced NF-κB and MMP-9 and increased E-cadherin expression).

Conclusion

The dual specificity of VGB for VEGFR1 and VEGFR2, through which the PI3K/AKT and MAPK/ERK1/2 signaling pathways can be abrogated and, subsequently, angiogenesis, tumor growth, and metastasis are inhibited.

General significance

This study demonstrated that simultaneous blockade of VEGFR1 and VEGFR2 downstream cascades is an effective means for treatment of various angiogenic disorders, especially cancer.  相似文献   
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