Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Sep 2014
The inhibitor of calcium/calmodulin-dependent protein kinase II KN93 attenuates bone cancer pain via inhibition of KIF17/NR2B trafficking in mice.
The N-methyl-d-aspartate receptor (NMDAR) containing subunit 2B (NR2B) is critical for the regulation of nociception in bone cancer pain, although the precise molecular mechanisms remain unclear. KIF17, a kinesin motor, plays a key role in the dendritic transport of NR2B. The up-regulation of NR2B and KIF17 transcription results from an increase in phosphorylated cAMP-response element-binding protein (CREB), which is activated by calcium/calmodulin-dependent protein kinase II (CaMKII). ⋯ These results showed that inoculation of osteosarcoma cells induced progressive bone cancer pain and resulted in a significant up-regulation of p-CaMKII, NR2B and KIF17 expression after inoculation. Intrathecal administration of KN93, a CaMKII inhibitor, down-regulated these three proteins and attenuated bone cancer pain in a dose- and time-dependent manner. These findings indicated that CaMKII-mediated KIF17/NR2B trafficking may contribute to bone cancer pain, and inhibition of CaMKII may be a useful alternative or adjunct therapy for relieving cancer pain.
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Pharmacol. Biochem. Behav. · Sep 2014
Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats.
Salidroside (SA) is the primary bioactive marker compound in the standardized extracts from Rhodiola rosea. Although it has potential antidepressant activity in a rat behavioral despair model, the mechanisms of antidepressant effect for SA remain unclear. The objective of this study was to evaluate the antidepressant effects of SA and to discuss the potential mechanisms in olfactory bulbectomized (OBX) rats. ⋯ The antidepressant mechanisms of SA might be associated with its anti-inflammatory effects and the regulation of HPA axis activity. Reversal of abnormalities of GR may be partly responsible for those effects. These findings suggested that SA might become a beneficial agent to prevent and treat the depression.
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Pharmacol. Biochem. Behav. · Sep 2014
Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats.
Depression and anxiety are common comorbidities of neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. ⋯ Tramadol reduced the immobility time in CCI rats by 22% (P<0.001), while having no effect on sham. Tramadol reversed the changes in mechanical sensitivity as well as anxiety-related and depression-associated behaviors that are caused by injury of the sciatic nerve with only minor effects in the absence of injury. These data suggest that tramadol relieves chronic pain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP.
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Pharmacol. Biochem. Behav. · Sep 2014
Antinociceptive effects of systemic tanshinone IIA on visceral and somatic persistent nociception and pain hypersensitivity in rats.
Previous studies showed that tanshinone IIA (TIIA), an important lipophilic component of Danshen, has been well-established to exhibit various neuroprotective actions in the nervous system. Although we previously reported that TIIA had a significant anti-nociceptive effect in complete Freund's adjuvant (CFA)-induced pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA in animals and the appropriate indications for treatment of clinical pain remain unclear. Therefore, in the present study, by using both somatic and visceral pain models, the antinociceptive and antihyperalgesic effects of TIIA were evaluated by intraperitoneal administration in rats. ⋯ Moreover, in the formalin test, the antinociception of TIIA was significant for both phases 1 and 2 in the pretreatment groups, but only effective for phase 2 in the post-treatment group. In the acetic acid writhing test, the number of writhes was effectively blocked by both pre- and post-treatment of TIIA. Taken together, these results provide a new line of evidence showing that TIIA is also able to produce analgesia against various 'phenotypes' of nociception and hypersensitivity.
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Pharmacol. Biochem. Behav. · Sep 2014
Valsartan reverses depressive/anxiety-like behavior and induces hippocampal neurogenesis and expression of BDNF protein in unpredictable chronic mild stress mice.
Valsartan is a synthetic non-peptide angiotensin II type 1 receptor antagonist that dilates blood vessels and reduces blood pressure by blocking the action of angiotensin, and is safe and well tolerated in hypertensive patients. Population-based studies have suggested a positive role of sartans in reducing the risk of depression. This study aimed at investigating the effects of valsartan on unpredictable chronic mild stress (UCMS) mice by means of open-field test (OFT), novel-suppressed feeding test (NSF), tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). ⋯ In this study, an impairment in hippocampal neurogenesis which parallelled with a reduced BDNF level in the hippocampus was observed in the mice that were treated with UCMS for 6 weeks. But the proliferation of progenitor cells and generation of new hippocampal neurons were restored after these mice were treated with valsartan (40 mg/kg/d, p.o.) for 4 weeks. These findings demonstrate that valsartan is an effective antidepressant/antianxiety reagent and can promote the hippocampal neurogenesis and expression of BDNF.