Pharmacology, biochemistry, and behavior
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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.
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Pharmacol. Biochem. Behav. · Sep 2014
Interaction between the dopaminergic and opioidergic systems in dorsal hippocampus in modulation of formalin-induced orofacial pain in rats.
The hippocampus is a region of the brain that serves several functions. The dopaminergic system acts through D1- and D2-like receptors to interfere in pain modulation and the opioid receptors play major roles in analgesic processes and there are obvious overlaps between these two systems. The present study investigated the interaction between the opioidergic and dopaminergic systems in the dorsal hippocampus (CA1) region for formalin-induced orofacial pain. ⋯ Sulpiride reversed the antinociceptive effects of morphine only in the first phase, but this result was not significant. Our findings suggest that there is cross-talk between the opioidergic and dopaminergic systems. Opioidergic neurons also exerted antinociceptive effects by modulation of the dopaminergic system in the CA1 region of the brain.
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Pharmacogenetic research has the potential to explain the variation in treatment efficacy within patient populations. Understanding the interaction between genetic variation and medications may provide a method for matching patients to the most effective therapeutic options and improving overall patient outcomes. ⋯ Genetic variants in OPRM1, particularly the non-synonymous polymorphism A118G, have been repeatedly associated with the efficacy of treatments for pain and various types of dependence. This review focuses on the current understanding of the pharmacogenetic impact of OPRM1, primarily with regard to the treatment of pain and addiction.
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Pharmacol. Biochem. Behav. · Jul 2014
Intrathecal injection of selected peptide Myr-RC-13 attenuates bone cancer pain by inhibiting KIF17 and NR2B expression.
Although bone cancer pain is a common intractable clinical symptom, its underlying mechanisms are still elusive. Accumulating evidence reveals that the N-methyl-D-aspartate (NMDA) receptor containing a 2B subunit (NR2B) in the spinal cord contributes to bone cancer pain. Our preliminary study demonstrated that intrathecal injection of fusion peptide Myr-RC-13 could disrupt spinal KIF17/mLin10 interaction, which is an essential component of KIF17-mediated NR2B transport. ⋯ In addition, repetitive spinal delivery of Myr-RC-13 relieved bone cancer-related mechanical allodynia and spontaneous pain behaviors, and down-regulated expression of spinal KIF17 and NR2B. Finally, our results demonstrated that selected peptide Myr-RC-13 was able to attenuate bone cancer pain via decreasing spinal KIF17 and NR2B expressions. Therefore, selected peptide Myr-RC-13 might be a potential analgesic strategy for bone cancer pain.
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Pharmacol. Biochem. Behav. · Jul 2014
Comparative StudyAntiallodynic and antihyperalgesic activity of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one compared to pregabalin in chemotherapy-induced neuropathic pain in mice.
Anticancer drugs - oxaliplatin (OXPT) and paclitaxel (PACLI) cause painful peripheral neuropathy activating Transient Receptor Potential (TRP) channels. Here we investigated the influence of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) and pregabalin on nociceptive thresholds in neuropathic pain models elicited by these drugs. Pharmacokinetics of LPP1 and its ability to attenuate neurogenic pain caused by TRP agonists: capsaicin and allyl isothiocyanate (AITC) were also investigated. ⋯ LPP1 and pregabalin reduce pain in OXPT and PACLI-treated mice. This activity of LPP1 might be in part attributed to the inhibition of TRPV1 and TRPA1 channels, but also central mechanisms of action cannot be ruled out.