Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jun 2017
The antidepressant-like effects of biperiden may involve BDNF/TrkB signaling-mediated BICC1 expression in the hippocampus and prefrontal cortex of mice.
Preclinical and clinical studies suggest that neuronal muscarinic acetylcholine receptor (M-AchR) antagonists have antidepressant-like properties. Despite the recent interest in bicaudal C homolog 1 gene (BICC1) as a target for the treatment of depression, the upstream signaling molecules that regulate BICC1 are unknown, and very few studies have addressed the involvement of BICC1 in the antidepressant-like effects of the selective M1-AchR inhibitor, biperiden. Growing evidence indicates that activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase receptor B (TrkB) signaling may be involved in antidepressant-like activities. ⋯ However, biperiden significantly alleviated the CUS-induced abnormalities. Moreover, we found that the effects of biperiden were antagonized by pretreatment with the TrkB antagonist K252a. Our results indicate that BDNF/TrkB signaling may be the major upstream mediator of BICC1 involvement in the antidepressant-like effects of biperiden.
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Pharmacol. Biochem. Behav. · Feb 2017
HYP-17, a novel voltage-gated sodium channel blocker, relieves inflammatory and neuropathic pain in rats.
Clinical and experimental studies suggest that voltage-gated sodium channels (VGSCs) play a key role in the pathogenesis of neuropathic pain and that blocking agents against these channels can be potentially therapeutic. In the current study, we investigated whether a novel compound, (-)-2-Amino-1-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)-propan-1-one(HYP-17), binds to VGSCs and evaluated its inhibitory effect on Na+ currents of the rat dorsal root ganglia (DRG) sensory neurons and its analgesic effect on inflammatory and neuropathic pain. HYP-17 (10μM) reduced both the tetrodotoxin-sensitive (TTX-S) and the TTX-resistant (TTX-R) currents in DRG sensory neurons. ⋯ Electrophysiological study showed that HYP-17 significantly attenuated the hyper-responsiveness of lumbar dorsal horn neurons. In addition, HYP-17 significantly reduced the levels of pp38MAPK and p-JNK in microglia and astrocytes, respectively, in the L4-L5 spinal dorsal horn. Therefore, our results indicate that HYP-17 has potential analgesic activities against nociceptive, inflammatory and neuropathic pain.
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Pharmacol. Biochem. Behav. · Feb 2017
WY-14643, a selective agonist of peroxisome proliferator-activated receptor-α, ameliorates lipopolysaccharide-induced depressive-like behaviors by preventing neuroinflammation and oxido-nitrosative stress in mice.
Depression is a common disease that afflicts one in six people at some points in life. Numerous hypotheses have been raised in past years, but the exact mechanism that can be used to explain the development of depression remains obscure. Recently, more and more attentions are being focused on neuroinflammation and oxidative stress in depression. ⋯ Further analysis showed that WY-14643 pretreatment not only inhibited the production of pro-inflammatory cytokines induced by LPS, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), but also prevented the LPS-induced enhancement of oxidative and nitrosative stress in the hippocampus and prefrontal cortex. In addition, the LPS-induced decreases in hippocampal and prefrontal cortical brain-derived neurotrophic factor (BDNF) levels were reversed by WY-14643 pretreatment. Taken together, our data provide further evidence to show that WY-14643 could be an agent that can be used to treat depression, and inhibition of neuroinflammation and oxido-nitrosative stress may be the potential mechanism for the antidepressive effect of WY-14643.
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Pharmacol. Biochem. Behav. · Nov 2016
Anti-allodynic effect of mangiferin in neuropathic rats: Involvement of nitric oxide-cyclic GMP-ATP sensitive K+ channels pathway and serotoninergic system.
The neurobiology of neuropathic pain is caused by injury in the central or peripheral nervous system. Recent evidence points out that mangiferin shows anti-nociceptive effect in inflammatory pain. However, its role in inflammatory and neuropathic pain and the possible mechanisms of action are not yet established. ⋯ Mangiferin-induced anti-allodynia was prevented by the intrathecal administration of L-NAME (100μg/rat, non-selective nitric oxide synthase inhibitor), ODQ (10μg/rat, inhibitor of guanylate-cyclase) and glibenclamide (50μg/rat, channel blocker of ATP-sensitive K+ channels). Moreover, methiothepin (30μg/rat, non-selective 5-HT receptor antagonist), WAY-100635 (6μg/rat, selective 5-HT1A receptor antagonist), SB-224289 (5μg/rat, selective 5-HT1B receptor antagonist), BRL-15572 (4μg/rat, selective 5-HT1D receptor antagonist) and SB-659551 (6μg/rat, selective 5-HT5A receptor antagonist), but not naloxone (50μg/rat, non-selective opioid receptor antagonist), were able to prevent mangiferin-induced anti-allodynic effect. These data suggest that the anti-allodynic effect induced by mangiferin is mediated at least in part by the serotoninergic system, involving the activation of 5-HT1A/1B/1D/5A receptors, as well as the nitric oxide-cyclic GMP-ATP-sensitive K+ channels pathway, but not by the opioidergic system, in the SNL model of neuropathic pain in rats.
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Pharmacol. Biochem. Behav. · Oct 2016
Agmatine ameliorates lipopolysaccharide induced depressive-like behaviour in mice by targeting the underlying inflammatory and oxido-nitrosative mediators.
Experimental and clinical evidence indicates that pro-inflammatory cytokines, oxidative stress and brain-derived neurotrophic factor (BDNF) signalling mechanisms play a role in the pathophysiology of depression. Agmatine is a neurotransmitter and/or neuromodulator that has emerged as a potential agent to manage diverse central nervous system disorders. Agmatine has been shown to exert antidepressant-like effect. ⋯ Agmatine pre-treatment at 40mg/kg ameliorated LPS-induced neuroinflammation by attenuating brain IL-1β and TNF-α level. In addition, agmatine pre-treatment also up-regulated the BDNF level in the HC. The present study shows that pre-treatment of agmatine is able to abolish the behavioural responses in the FST and TST elicited by the LPS-induced model of depression that may depend on the inhibition of pro-inflammatory mediators, reduction of oxidative stress as well as activation neuroplasticity-related signalling in mice, suggesting that agmatine may constitute an monotherapy/adjuvant for the management of depression associated with inflammation.