Neuroscience
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Chronic stress, the administration of glucocorticoids and the prolonged activation of glucocorticoid receptors (GRs) are reported to induce affective changes in humans and rodents that resemble a depressive state. However, data concerning the behavioral and molecular effects of the selective activation of specific GRs are limited, and the conclusions derived remain debatable. In this study, our goal was to investigate the behavioral and molecular changes following the prolonged activation of GRs in mice via exposure to the specific agonist dexamethasone (DEX). ⋯ Furthermore, our results indicate a decrease in the mRNA expression of glutamate aspartate transporter (GLAST, Slc1a3), an astroglial cell marker, in the hippocampus and prefrontal cortex. These results demonstrate that the prolonged activation of GR receptors induced a depression-like state in mice, activated stress-related genes and induced a decrease in the mRNA expression of GLAST, an astroglial marker, in the prefrontal cortex and hippocampus. Together, the results reported here challenge several hypotheses concerning the role of GRs in the development of behavioral and molecular alterations relevant to stress-related disorders, such as depression, under the same experimental conditions.
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In the dorsal facial area (DFA) of the medulla, an activation of either P2 purinergic receptor or nitric oxide synthase (NOS) results in the release of glutamate, leading to an increase in blood flow of the common carotid artery (CCA). It is not known whether activation of the P2 receptor by ATP may mediate activation of NOS/guanylyl cyclase to cause glutamate release and/or whether L-Arg (nitric oxide (NO) precursor) may also cause ATP release from any other neuron, to cause an increase in CCA flow. We demonstrated that microinjections of P2 receptor agonists (ATP, α,β-methylene ATP) or NO precursor (L-arginine) into the DFA increased CCA blood flow. ⋯ In conclusion, ATP activation of the P2 receptor in the DFA induced activation of neuronal NOS/guanylyl cyclase, which causes glutamate release leading to an increase in CCA blood flow. However, arginine activation of neuronal NOS/guanylyl cyclase, which also caused glutamate release and CCA blood flow increase, did not induce activation of P2 receptors. These findings provide important information for drug design and/or developing therapeutic strategies for the diseases associated with CCA blood flow that supplies intra- and extra-cranial tissues.
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The amygdala, prefrontal cortex, striatum and other connected forebrain areas are important for reward-associated learning and subsequent behaviors. How these structurally and functionally dissociable regions are recruited during initial learning, however, is unclear. Recently, we showed amygdalar nuclei were differentially recruited across different stages of cue-food associations in a Pavlovian conditioning paradigm. ⋯ Furthermore, within the perifornical lateral hypothalamus, tone-food pairings selectively recruited neurons that produce the orexigenic neuropeptide orexin/hypocretin. These data show a functional map of the forebrain areas recruited by appetitive associative learning and dependent on experience. These selectively activated regions include interconnected prefrontal, striatal, and hypothalamic regions that form a discrete but distributed network that is well placed to simultaneously inform cortical (cognitive) processing and behavioral (motivational) control during cue-food learning.
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Prenatal exposure to lipopolysaccharide (LPS) or high-fat diet (HFD) results in hippocampal impairment and cognitive deficits in offspring rats. What is not clear is how prenatal exposure to LPS combined with pre- and post-natal HFD would affect the hippocampus in offspring rats. ⋯ Prenatal exposure to LPS combined with pre- and post-natal HFD result in a protective effect on the hippocampus in offspring rats, and it might be a benefit from the predictive adaptive response to prenatal inflammation.
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We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens μ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens μ-opioid receptor mechanisms in capsaicin-induced analgesia. ⋯ Intra-accumbens injection of the μ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens μ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain.