Brain research
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Gastric electrical stimulation (GES) has been suggested as a therapy for patients with gastric motility disorders or morbid obesity. However, it is unclear whether GES also affects intestinal sensory and motor functions. Furthermore, little is known about intraspinal visceroreceptive transmission and processing for duodenal afferent information. ⋯ Resiniferatoxin (2.0 microg/kg, i.v.), an ultrapotent agonist of transient receptor potential vanilloid receptor-1 (TRPV1), abolished DD responses and GES effects on all neurons examined in vagotomized rats. Additionally, 29/33 (88%) DD-responsive neurons received inputs from somatic receptive fields on the back, flank and medial/lateral abdominal areas. It was concluded that GES mainly exerted an excitatory effect on T9-T10 spinal neurons with duodenal input transmitted by sympathetic afferent fibers expressing TRPV1; spinal neuronal responses to GES were strengthened with an increased pulse width and/or frequency of stimulation; T9-T10 spinal neurons processed input from the duodenum and might mediate effects of GES on duodenal sensation and motility.
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Alcohols and volatile anesthetics modulate the function of cys-loop ligand-gated ion channels, binding to a putative site between transmembrane domains two and three. The extracellular linker between these two domains is important in the transduction of the gating signal from the glycine binding site to the channel gate. Although the anesthetic binding site is proposed to be in the same region throughout the cys-loop receptor family, the modulatory effects of these compounds depend on the receptor. ⋯ Mutation at this residue did not affect thiol binding to residues in TM2 or TM3 and it does not appear that residue 281 constitutes part of the alcohol binding site. The K281P receptors displayed constitutive activity in the absence of glycine, and unlike wild-type receptors, this channel opening was antagonized by application of either volatile anesthetics or another GlyR modulator, zinc. Our data suggest that the TM2-TM3 extracellular loop plays a role in the transduction of signals generated by allosteric modulators in addition to gating signals that follow glycine binding.
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Conditioned taste aversions (CTAs) may be acquired when an animal consumes a novel taste (conditioned stimulus; CS) and then experiences the symptoms of poisoning (unconditioned stimulus; US). Animals will later avoid the taste that was previously associated with malaise. Extinction of a CTA is observed following repeated, non-reinforced exposures to the CS and represents itself as a resumption of eating/drinking the once-avoided tastant. ⋯ Low levels of c-Fos expression in the central nucleus of the amygdala (CE) were observed throughout EXT with little change in expression detectable following SR. These measurements reflect the dynamic nature of brain activity during acquisition and extinction of a CTA and highlight an important role for cortical neurons in the brain reorganization that occurs during SR of a CTA. The data also suggest that certain sub-nuclei of the AMY may play a relatively minor role in SR of this defensive reaction to a learned fear.
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Cannabinoids, such as anandamide, are involved in pain transmission. We evaluated the effects of AM404 (N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide), an anandamide reuptake inhibitor, monitoring the expression of c-fos, a marker of activated neurons and the pain-related behaviours using formalin test. The study was carried out in an experimental model of inflammatory pain made by a single injection of formalin in rat hind paws. ⋯ We found that Fos-positive neurons in dorsal superficial and deep laminae of the lumbar spinal cord increased in formalin-injected animals and that AM404 significantly reduced Fos induction. Co-administration of cannabinoid CB(1) receptor antagonist (AM251), cannabinoid CB(2) receptor antagonist (AM630) and transient receptor potential vanilloid type 1 (TRPV-1) antagonist (capsazepine), attenuate the inhibitory effect of AM404 and this effect was higher using cannabinoid CB(2) and vanilloid TRPV-1 receptor antagonists. These results suggest that AM404 could be a useful drug to reduce inflammatory pain in our experimental model and that cannabinoid CB(2) receptor and vanilloid TRPV-1 receptor, and to a lesser extent, the cannabinoid CB(1) receptor are involved.
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Enhancement of the glutamatergic excitatory synaptic transmission efficacy in the FeCl3 induced epilepsy model is associated with changes in the levels of glutamate and GABA transporter proteins. This study examined the effect of levetiracetam (LEV) on glutamate overflow and glutamate/GABA transporters expression in rats with epileptogenesis induced by the amygdalar injection of 1.0 microl of 100 mM FeCl3 (epileptic rat) and in control rats receiving amygdalar acidic saline injection (non-epileptic rat). In amygdalar acidic saline injected rats, 40 mM KCl-evoked glutamate overflow was significantly suppressed by both 32 and 100 microM LEV co-perfusion. ⋯ The increased expression of EAAC-1 and the decreased expression of GTRAP3-18 in association with the up-regulation of GAT-3 due to such continual LEV administration was thus found to enhance GABA synthesis and reverse the transport of GABA both in non-epileptic and epileptic rats. The suppression of glutamate excitation and the enhancement of GABA inhibition in the rats with continual LEV administration is a result of the up-regulation of glutamate and GABA transporters with the down-regulation of GTRAP3-18. These observations together demonstrated the critical molecular mechanism of the anti-epileptic activity of LEV.