Neuroscience
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Cholecystokinin (CCK) is a neuropeptide widely distributed in the mammalian brain. This peptide regulates many physiological functions and behaviors, such as cardio-respiratory control, thermoregulation, nociception, feeding, memory processes and motivational responses, and plays a prominent role in emotional responses including anxiety and depression. CCK-expressing brain regions involved in these functions remain unclear and their identification represents an important step towards understanding CCK function in the brain. ⋯ This procedure efficiently reduced CCK levels locally. shCCK-treated animals showed reduced levels of anxiety in the elevated plus-maze, and lower despair-like behavior in the forced swim test. Our data demonstrate that CCK expressed in the BLA represents a key brain substrate for anxiogenic and depressant effects of the peptide. The study also suggests that elevated amygdalar CCK could contribute to panic and major depressive disorders that have been associated with CCK dysfunction in humans.
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Status epilepticus (SE) induced by pilocarpine or kainate is associated with yet not systemically investigated astrocytic and vascular injuries. To investigate their possible association with neuronal damage, the changes in glial fibrillary acidic protein (GFAP), laminin and neuron-specific nuclear protein (NeuN) immunoreactivities were analyzed in rats treated with pilocarpine (380 mg/kg) or kainate (15 mg/kg), and receiving diazepam (20mg/kg) after 10 min of SE. A different group of rats was injected with endothelin-1 (ET-1) in the caudate putamen to reproduce the changes in GFAP and laminin immunoreactivities associated with ischemia. ⋯ The amygdala and submedius thalamic nucleus in the pilocarpine group, and the perirhinal and entorhinal cortices in the kainate group, also presented ischemic-like changes. These results indicate that laminin immunoreactivity is upregulated in the basal lamina of blood vessels after SE induced by pilocarpine or kainate. This phenomenon is significantly associated with lesions involving more glial than neuronal cells, in specific cerebral regions.
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Ghrelin is an orexigenic stomach peptide previously found to be important for the full display of anticipatory locomotor activity and hypothalamic neuronal activation that precedes a daily scheduled meal in mice. Ghrelin is also important for food-related motivation and seems to have direct effects in the mesocorticolimbic dopamine reward system. Here we hypothesized that neuronal activation in reward-related areas in anticipation of a scheduled meal could be mediated by elevated ghrelin induced by scheduled feeding, and therefore this would be attenuated in ghrelin receptor knock-out (GHSR KO) animals. ⋯ In addition, our results show a reduction in the proportion of activated orexin-immunoreactive (IR) neurons in GHSR KO animals in anticipation of the scheduled meal in comparison to the proportion of activated orexin neurons in wild type (WT) mice. Interestingly we observed that both GHSR and ghrelin KO mice had fewer orexin-IR cells than their WT littermates suggesting that lack of ghrelin or sensitivity to ghrelin may play a role in the development of the orexin system. Our data also suggest that ghrelin may mediate food anticipation, in part, by stimulating both the orexin system and the mesolimbic reward system.
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This study was carried out on decerebrate, paralyzed and artificially ventilated cats to investigate the central regulatory mechanism for cough reflex. Fictive cough was induced by repetitive stimulation of the superior laryngeal nerve (SLN) or the nucleus tractus solitarius (NTS), and characterized by an increased inspiratory discharge in the phrenic nerve (stage 1 of cough; S1C) and large burst discharge in the iliohypogastric nerve (stage 2 of cough; S2C). Membrane potential was recorded from the neurons located in the cough-inducible sites of the NTS. ⋯ Group II neurons with the DD-type response may integrate the tussigenic afferent information and send a gate signal to the cough pattern generator. Group III neurons with either DH-type or HH-type response may constitute the network of cough pattern generation or modulatory circuits recruited during the cough reflex. The present study suggests that Group II neurons may play a gating role in generating the cough reflex.
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Convergent evidence indicates that raphestriatal serotonin (5-HT) neurons can convert and release dopamine (DA) derived from exogenous administration of the pharmacotherapeutic L-3,4-dihydroxyphenyl-L-alanine (L-DOPA) as a treatment for Parkinson's disease (PD). While aspects of such neuroplasticity may be beneficial, chronic L-DOPA may also modify native 5-HT function, precipitating the appearance prevalent non-motor PD symptoms such as anxiety and depression. To examine this, male Sprague-Dawley rats were rendered parkinsonian with bilateral medial forebrain bundle 6-hydroxydopamine (6-OHDA) infusions and treated for at least 28 days with vehicle or L-DOPA. ⋯ Behaviorally, rats could only be tested 24h after their last L-DOPA injection due to severe dyskinesia. Despite this, prior exposure to chronic L-DOPA treatment exerted a pronounced anxiogenic phenotype. Collectively, these results suggest that chronic L-DOPA treatment may interfere with the balance of DA and 5-HT function in affect-related brain regions and could induce and/or exacerbate non-motor symptoms in PD.