Neuroscience
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We have conducted the first study of sleep in the platypus Ornithorhynchus anatinus. Periods of quiet sleep, characterized by raised arousal thresholds, elevated electroencephalogram amplitude and motor and autonomic quiescence, occupied 6-8 h/day. The platypus also had rapid eye movement sleep as defined by atonia with rapid eye movements, twitching and the electrocardiogram pattern of rapid eye movement. ⋯ This suggests that the low-voltage electroencephalogram is a more recently evolved feature of mammalian rapid eye movement sleep. Rapid eye movement sleep occupied 5.8-8 h/day in the platypus, more than in any other animal. Our findings indicate that rapid eye movement sleep may have been present in large amounts in the first mammals and suggest that it may have evolved in pre-mammalian reptiles.
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The amygdala is a complex forebrain structure proposed to play a pivotal role in fear conditioning circuitry. In this study, c-Fos immunomapping was applied to investigate the functional activation of particular amygdalar nuclei following a 50-trial training session of two-way active avoidance reaction. To dissect distinctive responses displayed by the animals and to cluster them into groups of correlated behaviors, factor analysis was employed. ⋯ The expression in the cortical nucleus correlated negatively with grooming behavior, whereas c-Fos immunolabeling of the other three subdivisions of the amygdala could be associated with the number of intertrial responses. No correlation was observed between c-Fos expression and avoidance reactions performed or the amount of shock received by the animal. The results obtained with c-Fos mapping of various regions of rat amygdala, combined with a fine dissection of behavioral repertoire, imply that there are specific functional links between particular parts of the structure and distinctive behaviors that reflect various emotional states of the animal.
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N-methyl-D-aspartate receptor activation regulates refractoriness of status epilepticus to diazepam.
Status epilepticus, prolonged intermittent or continuous seizure activity lasting 30 min or longer, is associated with high morbidity and mortality. The longer a seizure persists, the more refractory to treatment it becomes. The pilocarpine model of status epilepticus in rodents develops refractoriness to many first-line treatments as seizure duration increases, rendering it a good model to study refractory status epilepticus. ⋯ The results indicate that N-methyl-D-aspartate receptor activation plays a role in the seizure-induced refractoriness to benzodiazepines in status epilepticus, and blocking N-methyl-D-aspartate receptor activation converts refractory status epilepticus to a seizure responsive to benzodiazepine therapy. These findings offer insights into developing novel therapeutic interventions to improve the treatment of status epilepticus. Understanding the molecular mechanisms that mediate the effects of N-methyl-D-aspartate receptor activation on the development of resistance to treatment in status epilepticus will provide rational insights into more rapid methods to terminate seizure activity in this condition.
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Opioids and receptor antagonists of excitatory amino acids attenuate mechanical allodynia and thermal hyperalgesia in animal models of neuropathic pain. Recently, a kainate receptor antagonist, 2S,4R-4-methylglutamate, has been developed but has not been tested for antinociceptive effects in animal models of neuropathic pain. We evaluated whether 2S,4R-4-methylglutamate attenuated responses to mechanical and thermal stimuli in uninjured (control) rats and increased responsiveness in rats with chronic constriction injury. ⋯ At four to eight days following chronic constriction injury, animals that displayed increased responsiveness to mechanical and thermal stimuli were injected intraperitoneally with either dizocilpine maleate (0.1 mg/kg), morphine (4 mg/kg), vehicle as controls, or 2S,4R-4-methylglutamate (25, 50, 75 or 100 mg/kg). 2S,4R-4-Methylglutamate (25, 50, 75 and 100 mg/kg) significantly attenuated the frequency of responses to mechanical stimuli (Wilcoxon, P < 0.05) and the latency of responses to thermal stimuli (analysis of variance and Duncan's, P < 0.05). Dizocilpine maleate and morphine, as expected, also reduced these responses. These results suggest that, in addition to opioid and N-methyl-D-aspartate receptors, kainate receptors may play a role in the maintenance of mechanical allodynia and thermal hyperalgesia associated with peripheral nerve injury.
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In previous studies we have shown that electrical stimulation of the nucleus submedius inhibits the rat radiant heat-induced tail flick reflex, and that this antinociceptive effect is mediated by the ventrolateral orbital cortex and periaqueductal gray. The aim of the present study was to examine whether electrical stimulation of the nucleus submedius could inhibit the rat jaw-opening reflex, and to determine whether electrolytic lesions of the ventrolateral orbital cortex or the periaqueductal gray could attenuate the nucleus submedius-evoked inhibition. Experiments were performed on pentobarbital-anesthetized rats. ⋯ The onset of inhibition occured 60 ms after the beginning of nucleus submedius stimulation and lasted about 100 ms, as determined by varying the conditioning-test time interval. Furthermore, ipsilateral lesions of the ventrolateral orbital cortex or bilateral lesions of the lateral or ventrolateral parts of periaqueductal gray eliminated the nucleus submedius-evoked inhibition of the jaw-opening reflex. These data suggest that the nucleus submedius plays an important role in modulation of orofacial nociception, and provide further support for a hypothesis that the antinociceptive effect of nucleus submedius stimulation is mediated by ventrolateral orbital cortex and activation of a descending inhibitory system in the periaqueductal gray.