Show simple item record  

dc.contributor.advisorKlockars, Anica
dc.contributor.advisorOlszewski, Pawel K.
dc.contributor.authorHead, Mitchell Antony
dc.date.accessioned2018-02-14T20:43:00Z
dc.date.available2018-02-14T20:43:00Z
dc.date.issued2017
dc.identifier.citationHead, M. A. (2017). Effect of novel ketamine-analogue R5 on brain activation and select behavioural parameters (Thesis, Master of Science (Research) (MSc(Research))). The University of Waikato, Hamilton, New Zealand. Retrieved from https://hdl.handle.net/10289/11652en
dc.identifier.urihttps://hdl.handle.net/10289/11652
dc.description.abstractKetamine is a common anaesthetic that works through complex neural mechanisms, including multiple molecular and circuitry targets. Importantly, it promotes analgesia, though it also induces undesirable effects, such as agitation, disorientation, hallucinations and nausea. Thus, there is an ongoing search for novel ketamine analogues that influence a similar repertoire of brain targets as ketamine, whose beneficial effects are potentiated. The present project, utilizing rats as an animal model, focused on examining functional properties of the ester-analogue of ketamine, R5, whose potentially beneficial profile had been suggested by preliminary studies. First, brain activation patterns following R5 compared to ketamine (and another ester-analogue control compound, R1) were assessed by employing immunohistochemical detection of an immediate-early gene product, c-Fos. R5 produced a somewhat similar pattern of activity as ketamine, whereas more profound differences in c-Fos were detected after R1. It was particularly striking in areas related to pain and addiction, including the anterior insular cortex (AIC) and paraventricular nucleus (PVN). Therefore, in the subsequent set of experiments, effects of R5 on pain- and addiction-related behavioral parameters were assessed in rats injected with R5 intracerebroventricularly (ICV) or intraparenchymally. It was found that BaCl attenuated ICV R5-induced analgesia. AIC administration of R5 produced modest analgesia in the tail-flick test. Finally, PVN R5 reduced naltrexone-precipitated exercise-induced withdrawal. In sum, R5 shows an analgesic effect similar to ketamine, most likely by targeting a similar subset of brain sites, which suggests that this particular ester-analogue can be considered as a good candidate for conceptualizing future pain management strategies.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherThe University of Waikato
dc.rightsAll items in Research Commons are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectanaesthetic
dc.subjectketamine
dc.subjectanalgesia
dc.subjectneuroscience
dc.subjectcannulation
dc.subjectcfos
dc.titleEffect of novel ketamine-analogue R5 on brain activation and select behavioural parameters
dc.typeThesis
thesis.degree.grantorThe University of Waikato
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (Research) (MSc(Research))
dc.date.updated2017-10-29T23:25:35Z
pubs.place-of-publicationHamilton, New Zealanden_NZ


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record