Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jul 2015
Involvement of nuclear factor kappa B in the maintenance of persistent inflammatory hypernociception.
The pathophysiology of chronic inflammatory pain remains poorly understood. In this context, we developed an experimental model in which successive daily injection of prostaglandin E2 (PGE2) for 14days into rat hind paws produces a persistent state of hypernociception (i.e. decrease in mechanical nociceptive threshold). This state persists for more than 30days after discontinuing PGE2 injection. ⋯ Treatment with antisense oligonucleotides against the NF-κB p65 subunit for 5 consecutive days also reduced persistent inflammatory hypernociception. Inhibition of PKA and PKCε reduced persistent inflammatory hypernociception, which was associated with inhibition of NF-κB p65 subunit translocation. Together these results suggest that peripheral activation of NF-κB by PKA and PKC in primary sensory neurons plays an important role in maintaining persistent inflammatory pain.
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Pharmacol. Biochem. Behav. · Jun 2015
Antidepressant-like effects of oleoylethanolamide in a mouse model of chronic unpredictable mild stress.
Oleoylethanolamide (OEA) is an endocannabinoid analog that belongs to a family of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of mental disorder-related behaviors. In this study, we examined whether OEA is effective against depression and investigated the role of circulating endogenous acylethanolamides during stress. ⋯ Our findings indicate that OEA normalized sucrose preferences, locomotion distances, rearing frequencies, prefrontal cortex and hippocampal atrophy, and adrenal indices. In addition, OEA reversed the abnormalities of BDNF and MDA levels and SOD activities in the hippocampus and prefrontal cortex, as well as changes in serum levels of ACTH, CORT, and T-AOC. The antidepressant effects of OEA may be related to the regulation of BDNF levels in the hippocampus and prefrontal cortex, antioxidant defenses, and normalizing hyperactivity in the hypothalamic-pituitary-adrenal axis (HPA).
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Pharmacol. Biochem. Behav. · May 2015
Clonidine ameliorates cognitive impairment induced by chronic cerebral hypoperfusion via up-regulation of the GABABR1 and GAD67 in hippocampal CA1 in rats.
Chronic cerebral hypoperfusion may cause cognitive impairment, but the underlying neurobiological mechanism is poorly understood. In this study, we investigated whether clonidine, an α2-adrenergic receptor agonist, could play neuroprotective role against chronic ischemic brain injury and the potential mechanism. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). ⋯ Our results showed that the cognitive function was partially impaired, and the expression of neuronal nuclei (NeuN), glutamic acid decarboxylase 67 (GAD67) and γ-aminobutyric acid-B receptor 1 (GABABR1) in hippocampal CA1 area was attenuated after 2VO, which were not observed in CA3 and dentate gyrus (DG). Administration of 0.05mg/kg clonidine (i.p.) for 7days could improve cognitive function and the expression of NeuN, GAD67 and GABABR1 in CA1, but did not affect the protein levels in CA3 and DG. These findings demonstrated that clonidine could ameliorate cognitive deficits and neuronal impairment induced by chronic cerebral hypoperfusion via up-regulation of GABABR1 and GAD67 in hippocampal CA1.
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Pharmacol. Biochem. Behav. · Apr 2015
The antinociceptive effect of stimulating the retrosplenial cortex in the rat tail-flick test but not in the formalin test involves the rostral anterior cingulate cortex.
The stimulation of the retrosplenial cortex (RSC) is antinociceptive in the rat tail-flick and formalin tests. The rat RSC is caudal to and send projections to the ipsilateral anterior cingulate cortex (ACC), which is also involved in pain processing. This study demonstrated that pre-treating the rostral (rACC), but not the caudal ACC with CoCl2 (1mM), or the rACC ablation increased the duration of the antinociceptive effect evoked by a 15-s period of electrical stimulation (AC, 60Hz, 20μA) of the RSC in the rat tail-flick. ⋯ This effect was similar in sham or stimulated animals at the RSC. We conclude that the antinociceptive effect of stimulating the RSC in the rat tail-flick test is modulated by the rACC involving GABA-A receptors in this cortex. In contrast, the antinociceptive effect of stimulating the RSC in the formalin test does not involve the rACC.
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Pharmacol. Biochem. Behav. · Mar 2015
Antinociceptive effect of intracerebroventricular administration of glycine transporter-2 inhibitor ALX1393 in rat models of inflammatory and neuropathic pain.
Glycinergic transmission has an important role in regulating nociception in the spinal cord. The glycine transporter-2 (GlyT2) is localized at presynaptic terminals of glycinergic neurons and eliminates glycine from the synaptic cleft to terminate glycinergic transmission. Systemic and intrathecal administration of GlyT2 inhibitors alleviate various types of pain. ⋯ In the CCI rats, ALX1393 inhibited mechanical and cold hyperalgesia in a dose-dependent manner. The antihyperalgesic effects of ALX1393 (100 μg) were reversed completely by i.c.v. pretreatment with a glycine receptor antagonist strychnine (10 μg). These results suggest that GlyT2 contributes to nociceptive transmission at supraspinal level and that the selective GlyT2 inhibitor is a promising candidate for the treatment of inflammatory and neuropathic pain without causing motor dysfunction.