PhD Agnieszka Nikiforuk

  • The effects of positive allosteric modulators of alpha7 nicotinic acetylcholine receptors on complex cognitive processes - 2013-07-12 - 2016-07-12
    α7 nicotinic acetylcholine receptors (α7-nAChRs) play important role in the regulation of complex cognitive functions which may be impaired in a number of psychiatric disorders. Moreover, it has been suggested that the α7-nAChRs may be implicated in the pathogenesis of schizophrenia. Therefore, in recent years, α7-nAChRs arouse a great interest as a target for the development of pharmacological treatment of cognitive dysfunctions in schizophrenia. The activity of α7-nAChR can be modulated be either orthosteric agonists or positive allosteric modulators (PAMs). Despite numerous preclinical evidences, the procognitive action of direct α7-nAChR agonist has not been conclusively confirmed in patients with schizophrenia. Allosteric modulation is thought to be associated with more favourable and more specific action. Hence, α7-nAChR PAMs may represent more promising tool. While several α7-nAChR PAMs have been recently developed, their behavioural effects, including their potential impact on cognitive processes, have not been yet extensively characterised. Our research hypothesis is based on the presumption that the action of PAMs may differ from the effects induced by orthosteric receptor activation. It is suggested by PAM-induced retardation of rapid desensitization, a fundamental feature of α7-nAchR. Therefore, the aim of the proposed project is to examine the effects of α7-nAChR PAM in comparison to orthosteric agonists in animal tasks assessing cognitive domains that are important from the perspective of cognitive deficits encountered in schizophrenia (e.g., executive functions, attention, and working memory).
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