The European journal of neuroscience
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The aim of the present study was to investigate the spinal cord effects and sites of action of different inhaled concentrations (0.5-2%) of the anaesthetic, halothane. Simultaneous recordings were made of 3 Hz, suprathreshold (1.5 x T) electrically evoked spinal dorsal horn (DH) wide-dynamic range (WDR) neuron responses and of single motor unit (SMU) electromyographic (EMG) responses underlying the spinal withdrawal reflex in spinalized Wistar rats. Compared with the baseline responses obtained with 0.5% halothane, the electrically evoked early responses of the DH WDR neurons as well as the SMUs were only depressed by the highest, 2% concentration of halothane. ⋯ The inhibitory effects of 2% halothane on the early and the late responses of the DH WDR neurons, but not of the SMUs, were completely reversed by opioid micro-receptor antagonist naloxone (0.04 mg/kg). However, no significant effects of naloxone were found on different responses of the DH WDR neurons as well as the SMUs at 0.5-1% halothane, suggesting that different concentrations of halothane may modulate different spinal receptors. We conclude that halothane at high concentrations (1.5-2%) seems to play a predominant inhibitory role via spinal multireceptors on ventral horn (VH) motor neurons, and less on DH sensory WDR neurons, of the spinal cord.
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The vanilloid TRPV1 receptor, present on primary afferent fibres, is activated by noxious heat, low pH and endogenous vanilloids. Changes in the function or distribution of TRPV1 receptors may play an important role in pain induced by inflammation or neuropathy. The aim of the present study was to evaluate the role of peripheral TRPV1 receptors in thermal nociception in rat models of inflammatory and neuropathic pain. ⋯ The higher dose of IRTX (0.4 microg) significantly (P<0.05) inhibited 45 degrees C-evoked responses in both inflamed and naïve rats. In sham-operated and SNL rats, IRTX (0.004 and 0.4 microg) significantly (P<0.05) inhibited 45 degrees C-evoked, but had no effect on mechanically evoked responses of WDR neurons. These data support the role of peripheral TRPV1 receptors in noxious thermal transmission in naïve, inflamed and neuropathic rats, and suggest that there is an increased functional contribution of peripheral TRPV1 receptors following acute inflammation.
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Comparative Study
Inhibitory effects of CB1 and CB2 receptor agonists on responses of DRG neurons and dorsal horn neurons in neuropathic rats.
Cannabinoid 2 (CB2) receptor mediated antinociception and increased levels of spinal CB2 receptor mRNA are reported in neuropathic Sprague-Dawley rats. The aim of this study was to provide functional evidence for a role of peripheral, vs. spinal, CB2 and cannabinoid 1 (CB1) receptors in neuropathic rats. Effects of the CB2 receptor agonist, JWH-133, and the CB1 receptor agonist, arachidonyl-2-chloroethylamide (ACEA), on primary afferent fibres were determined by calcium imaging studies of adult dorsal root ganglion (DRG) neurons taken from neuropathic and sham-operated rats. ⋯ Spinal ACEA inhibited mechanically evoked responses of neuropathic and sham-operated rats, these effects were blocked by SR141716A (0.01 microg/50 microL). Our data provide evidence for a functional role of CB2, as well as CB1 receptors on DRG neurons in sham and neuropathic rats. At the level of the spinal cord, CB2 receptors have inhibitory effects in neuropathic, but not sham-operated rats suggesting that spinal CB2 may be an important analgesic target.
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It is well-established that light pulses regulate components of the extracellular signal-regulated kinases I/II (ERK) cascade in the suprachiasmatic nuclei (SCN) circadian clock. These events are important for photic-resetting of the circadian clock. The SCN circadian clock is also reset by pulses of dark, but it is unknown if this stimulus alters the activity of ERK, the transcription factor Elk-1 or expression of the immediate early gene c-fos in the SCN. ⋯ When given at the beginning of the subjective night (CT13), a 6-h dark pulse did not phase-shift behavioural rhythms and failed to alter the expression of c-Fos, P-ERK, or P-Elk-1 in the SCN. At the level of the visual thalamus, expression of c-Fos in the intergeniculate leaflet was higher during the subjective night as compared to the subjective day, although dark pulses had no robust effects on expression of c-Fos or P-ELK-1 in this structure. We conclude that dark-pulse resetting of the circadian clock is complex and involves both non-photic and photic components.
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Comparative Study
Roles of NMDA receptor NR2A and NR2B subtypes for long-term depression in the anterior cingulate cortex.
The anterior cingulate cortex (ACC) is thought to be important for the establishment, consolidation and retrieval of permanent memory. In many brain regions, including the hippocampus, it is suggested that long-term potentiation (LTP) and long-term depression (LTD), the cellular mechanisms for learning and memory, require the activation of glutamate N-methyl-D-aspartate receptors (NMDARs). In the hippocampus, the NR2A subunit is believed to be involved in the induction of LTP, whereas the NR2B subunit contributes to the formation of LTD. ⋯ Here we show that LTD can be induced by the combination of presynaptic stimulation with postsynaptic depolarization ('pairing training') in adult mouse ACC neurons. This form of LTD is an NMDAR- and voltage-dependent mechanism and a postsynaptic Ca2+ increase is required for the induction of LTD. Furthermore, our studies provide direct physiological evidence that both NR2A and NR2B subunits are involved in the induction of LTD in the ACC.