Neuroscience
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Respiratory depression is the most well-known and dangerous side-effect of opioid analgesics. Clinical investigations have revealed that this opioid-induced respiratory depression is less severe in patients with chronic pain, but the mechanisms that underlie this phenomenon are unknown. Therefore, the present study was designed to examine the influence of chronic pain on morphine-induced respiratory depression. ⋯ Moreover, treatment with the 5-HT4 receptor agonist mosapride antagonized the morphine-induced decrease in minute volume, due to the enhancement of tidal volume. Finally, the expression of 5-HT4a receptor in the brainstem was enhanced in nerve-ligated mice compared to that in sham-operated mice. These results suggest that the decrease in morphine-induced respiratory depression under chronic pain is mediated by the enhancement of 5-HT4a receptor systems in the brainstem.
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Neuronal cell death induced by anaesthetics in the developing brain was evident in previous pre-clinical studies. However, the neuronal cell types involved in anaesthesia-induced neuronal cell death remains elusive. The aim of this study was to investigate glutamatergic, GABAergic, cholinergic and dopaminergic neuronal cell apoptosis induced by anaesthetic exposure in specific brain regions in rats. ⋯ In the cingulate cortex, 30% and 37% of apoptotic cells were GABAergic and glutamatergic neurons respectively. In the substantia nigra, 22% of apoptotic cells were dopaminergic neurons. Our data suggests, anaesthetic exposure significantly increases neuroapoptosis of glutamatergic, GABAergic and dopaminergic neurons in the developing brain but not that of the cholinergic neurons in the basal forebrain.
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Chronic restraint stress produces morphological changes in medial prefrontal cortex and disrupts a prefrontally mediated behavior, retrieval of extinction. To assess potential physiological correlates of these alterations, we compared neural activity in infralimbic and prelimbic cortex of unstressed versus stressed rats during fear conditioning and extinction. After implantation of microwire bundles into infralimbic or prelimbic cortex, rats were either unstressed or stressed via placement in a plastic restrainer (3 h/day for 1 week). ⋯ In infralimbic cortex, neurons in unstressed rats exhibited increased firing in response to the CS, whereas stressed rats showed no increase in infralimbic firing during the tone. Finally, CS-related firing in infralimbic but not prelimbic cortex was correlated with extinction retrieval. Thus, the stress-induced alteration of neuronal activity in infralimbic cortex may be responsible for the stress-induced deficit in retrieval of extinction.