Neuroscience
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Changes in the signaling of wide dynamic range neurons and the expression of glutamate transporters in the lumbar spinal dorsal horn of rats with Taxol-induced hyperalgesia are detailed in this report. Deep spinal lamina neurons have significantly increased spontaneous activity and after-discharges to noxious mechanical stimuli, increased responses to both skin heating and cooling, and increased after-discharges and abnormal windup to transcutaneous electrical stimuli. ⋯ These results suggest a state of increased excitability develops in spinal pain-signaling neurons as a consequence of decreased glutamate clearance. These changes in dorsal horn neurobiology likely in turn contribute to the hyper-responsiveness to sensory stimuli seen in animals treated with Taxol and may play a role in the pain seen in cancer patients receiving Taxol.
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Food intake is regulated by signals from the gastrointestinal tract. Both stimulation and inhibition of food intake may be mediated by upper gastrointestinal tract hormones, e.g. ghrelin and cholecystokinin that act at least partly via vagal afferent neurones. We now report that vagal afferent neurones in both rat and man express melanin-concentrating hormone and its receptor, melanin-concentrating hormone-1R. ⋯ The cholecystokinin-1 receptor antagonist lorglumide inhibited food-induced down-regulation of melanin-concentrating hormone and melanin-concentrating hormone-1R. We conclude that the satiety hormone cholecystokinin acts on vagal afferent neurones to inhibit expression of melanin-concentrating hormone and its receptor. Since the melanin-concentrating hormone system is associated with stimulation of food intake this effect of cholecystokinin may contribute to its action as a satiety hormone.
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The GABAB receptors are generally considered to be classical Gi-coupled receptors that lack the ability to mobilize intracellular Ca2+ without the aid of promiscuous G proteins. Here, we report the ability of GABAB receptors to promote calcium influx into primary cultures of rat cortical neurons and transfected Chinese hamster ovary cells. Chinese hamster ovary cells were transfected with GABAB1(a) or GABAB1(b) subunits along with GABAB2 subunits. ⋯ The selective store-operated channel inhibitor 1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole hydrochloride prevented increases in intracellular Ca2+ levels as did performing the assays in Ca2+ free buffers. In conclusion, GABAB receptors expressed in Chinese hamster ovary cells and endogenously expressed in rat cortical neurons promote Ca2+ entry into the cell via the activation of store-operated channels, using a mechanism that is dependent on Gi/o heterotrimeric proteins and phospholipase Cbeta. These findings suggest that the neuronal effects mediated by GABAB receptors may, in part, rely on the receptor's ability to promote Ca2+ influx.
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Fear-conditioned analgesia is an important survival response which is expressed upon re-exposure to a context previously paired with a noxious stimulus. The aim of the present study was to characterize further the behavioral, monoaminergic and hypothalamo-pituitary-adrenal axis alterations associated with expression of fear-conditioned analgesia. Rats which had received footshock conditioning 24 h earlier, exhibited reduced formalin-evoked nociceptive behavior upon re-exposure to the footshock chamber, compared with non-footshocked formalin-treated rats. ⋯ These data extend behavioral characterization of the phenomenon of fear-conditioned analgesia and suggest that measurement of ultrasound emission may be used as an ethologically relevant index of the defense response during fear-conditioned analgesia. Ultrasonic vocalization may also be a useful behavioral output to aid separation of nociception and aversion. The data provide evidence for discrete alterations in dopaminergic activity in the periaqueductal gray and thalamus and for altered hypothalamo-pituitary-adrenal axis activity following expression of defensive behavior.
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Comparative Study
Fatty acids differentially affect serotonin receptor and transporter binding in the rat brain.
The aim of this study was to examine the influence of different fat diets on serotonin receptor and transporter binding. Male Sprague-Dawley rats were fed a diet of either high saturated fat, omega-6 polyunsaturated fatty acid, omega-3 polyunsaturated fatty acid or low fat (control) for eight weeks. ⋯ Overall, the omega-6 polyunsaturated fatty acid diet exerted the most influence on serotonin receptor and transporter binding. These results may be of importance in relation to neuropsychiatric diseases such as schizophrenia, where associations between altered fatty acid levels and the serotonergic system have been made.