The inflammatory process, orchestrated against a variety of injurious stimuli, is composed of three inter-related phases; initiation, propagation and resolution. Understanding the interplay between these three phases and harnessing the beneficial properties of inflammation whilst preventing its damaging effects, will undoubtedly lead to the advent of much needed therapies, particularly in chronic disease states. The P2X7 receptor (P2X7R) is increasingly recognised as an important cell surface regulator of several key inflammatory molecules including IL-1β, IL-18, TNF-α and IL-6. Moreover, as P2X7R-dependent cytokine production is driven by activating the inflammasome, antagonists of this receptor are likely to have therapeutic potential as novel anti-inflammatory therapies. The function of the P2X7R in inflammation, immunity and its potential role in disease will be reviewed and discussed.
In humans, nicotine has been shown to improve attention in both normal and impaired individuals. Observations in rats reflect some, but not all aspects of the nicotine-induced improvements in humans. To date these findings have not been replicated in mice. To examine the effect of nicotine on sustained attention in mice, we have established a version of the 5-choice serial reaction-time (5-CSR) task with graded levels of difficulty, based upon spatial displacement and a variable intertrial interval. Using this paradigm, microgram doses of nicotine produced a consistent reduction in the level of omissions and an improvement in proportion correct in normal mice. This improvement in sustained attention was made irrespectively of whether mice had previously received nicotine. In an attempt to elucidate which nicotinic acetylcholine receptor (nAChR) subtype(s) mediate this effect, we examined the performance of a7 nAChR knockout (KO) mice in the 5-CSR task. a7 nAChR KO mice not only acquired the task more slowly than their wild-type littermates, but on attaining asymptotic performance, they exhibited a higher level of omissions. In conclusion, by increasing the level of task difficulty, the performance of mice was maintained at sufficiently low levels to allow a demonstrable improvement in performance upon nicotine administration. Furthermore, as a7 KO mice are clearly impaired in the acquisition and asymptotic performance of this task, the a7 nAChR may be involved in mediating these effects of nicotine.
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