Neuropharmacology
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The objective of the present work was to study the effects of an early-life stress (maternal separation, MS) in the excitatory/inhibitory ratio as a potential factor contributing to the ageing process, and the purported normalizing effects of chronic treatment with the antidepressant venlafaxine. MS induced depressive-like behaviour in the Porsolt forced swimming test that was reversed by venlafaxine, and that persisted until senescence. Aged MS rats showed a downregulation of vesicular glutamate transporter 1 and 2 (VGlut1 and VGlut2) and GABA transporter (VGAT) and increased expression of excitatory amino acid transporter 2 (EAAT2) in the hippocampus. ⋯ Chronic treatment with corticosterone recapitulated the main biochemical findings observed in MS. The different effects that chronic stress exerts in young and adult animals on expression of proteins responsible for glutamate/GABA cycling may explain the involvement of glucocorticoids in ageing-related diseases. Modulation of glutamate/GABA release may be a relevant component of the therapeutic action of antidepressants, such as venlafaxine.
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The endocannabinoid anandamide (AEA) activates also transient receptor potential vanilloid-1 (TRPV1) channels. However, no data exist on the potential role of spinal TRPV1 activation by AEA in neuropathic pain. We tested the effect of: 1) AEA (5-100 μg), alone or in the presence of an inhibitor of its hydrolysis, and 2) elevated levels of endogenous AEA (following inhibition of AEA hydrolysis), in CCI rats, and the involvement of TRPV1 or cannabinoid CB(1) receptors in the observed effects. ⋯ Spinal AEA levels were increased after CCI, slightly increased further by URB597, 10 μg i.t., and strongly elevated by URB597, 100 μg. Injection of AEA (50 μg) into the lumbar spinal cord led to its dramatic elevation in this tissue, whereas, when a lower dose was used (5 μg) AEA endogenous levels were elevated only in the presence of URB597 (5 μg). We suggest that spinal AEA reduces neuropathic pain via CB(1) or TRPV1, depending on its local concentration.
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Numerous rodent and human studies have demonstrated that neuropeptide Y (NPY) is involved in the regulation of anxiety-related behaviors. In this study, we examined whether there were differences in NPY signaling between two inbred mouse strains (C57BL/6J and DBA/2J) that exhibit divergent basal and stress-induced anxiety phenotypes. We focused on the bed nucleus of the stria terminals (BNST), a structure in the extended amygdala that is important for the regulation of anxiety-like behavior and contains NPY receptors. ⋯ Ten days of chronic restraint stress increased basal GABAergic transmission and decreased NPY's ability to inhibit evoked GABAergic transmission in the dorsolateral BNST (dlBNST) via Y2R in DBA/2J, but not C57BL/6J, mice. Additionally, restraint stress increased NPY and Y2R expression across subregions of the BNST of DBA/2J mice 24 h after the last stress exposure, but no changes were observed in C57BL/6J mice. Together, these results suggest that chronic restraint stress engages the NPY system and alters NPY modulation of inhibitory transmission in the dlBNST of DBA/2J mice, but not C57BL/6J mice, which may be related to increased expression of anxiety-related behaviors in this strain.
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Prenatal ethanol exposure can damage the developing nervous system, producing long-lasting impairments in both brain structure and function. In this study we analyzed how exposure to this teratogen during the period of brain development affects the intracellular redox state in the brain as well as the development of anxiety- and depressive-like phenotypes. Furthermore, we also tested whether aerobic exercise might have therapeutic potential for fetal alcohol spectrum disorders (FASD) by increasing neuronal antioxidant capacity and/or by alleviating ethanol-induced behavioral deficits. ⋯ Levels of lipid peroxidation and protein oxidation were significantly increased in the hippocampus and cerebellum of ethanol-exposed rats, and there was a concomitant reduction in the levels of the endogenous antioxidant glutathione. Voluntary exercise was able to reverse the deficits in glutathione both in ethanol-exposed males and females. Thus, while voluntary physical exercise increased glutathione levels in both sexes, its effects at the behavioral level were sex dependent, with only ethanol-exposed male runners showing a decrease in depressive-like behaviors.
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Curcumin, a phenolic compound present in Curcuma longa, has been reported to exert antinociceptive effects in some animal models, but the mechanisms remain to be elucidated. This work aimed to investigate the antinociceptive action of curcumin on neuropathic pain and the underlying mechanism(s). Chronic constriction injury (CCI), a canonical animal model of neuropathic pain, was produced by loosely ligating the sciatic nerve in mice and von Frey hair or hot plate test was used to assess mechanical allodynia or thermal hyperalgesia (to heat), respectively. ⋯ Collectively, these findings indicate that the descending monoamine system (coupled with spinal β(2)-adrenoceptor and 5-HT(1A) receptor) is critical for the modality-specific antinociceptive effect of curcumin in neuropathic pain. Delta- and mu-opioid receptors are likely rendered as downstream targets, accordingly. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.