This thesis consisted of experiments designed to explore the construct of attention and investigate the disruptive effects of psychotomimetics, with a specific focus on NMDA antagonists. Phencyclidine (PCP) was administered through a variety of treatment regimens in order to to determine the ability of inducing cognitive-specific disruptions in attentional functioning. The hypothesis that sub-chronic exposure to PCP would result in persistent attentional impairment was tested, using the 5-choice serial reaction time task (5-CSRTT). The 5-CSRTT assesses not only visuospatial attention, but also components of impulsivity, compulsivity, speed of processing and motivation. It was determined that an additional task-related intervention that increased the attentional load was required to elucidate attentional impairment following sub-chronic PCP treatment.
The ability of rats to perform the modified version of the 5-CSRTT, known as the 5-choice continuous performance test (5C-CPT), was investigated. The 5C-CPT was implemented to provide a task that may have greater analogy to the human CPT, than the original 5-CSRTT. The consequence of dopaminergic D1 system activation was investigated. It was revealed that D1 partial agonism improved attentional performance in a baseline-dependent manner.
Following successful acquisition of the task, it was shown that repeated PCP treatment induced cognitive disruption that was cognitive-specific, and not confounded by generalised response disruption. Furthermore, a partial attenuation of the PCP-induced performance disruption was achieved following administration of the D1 partial agonist, SKF 38393. Moreover, sub-chronic PCP treatment was shown to impair 5C-CPT performance in the drug-free state. However, an additional challenge that further increased the attentional load was needed to elucidate a performance deficit. This highlighted that sustained attention/vigilance is sensitive to persistent impairment following sub-chronic PCP administration in a manner consistent with deficits observed in schizophrenia patients.
This prompted the investigation that tested the hypothesis that sub-chronic PCP treatment could induce enduring structural deficits in regions associated with attentional performance. Magnetic resonance imaging (MRI) was conducted, in conjunction with 5-CSRTT and pre-pulse inhibition (PPI). It was revealed that sub-chronic PCP treatment resulted in morphological brain abnormalities in brain regions associated with 5-CSRTT performance. This was coupled with deficits in sustained attentional performance following an increase in attentional load, yet PPI was unaffected. Taken together, these findings suggested sub-chronic PCP treatment impairs attentional functionality, an effect that dissociates between effortful and passive attentional processes.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/5441 |
| Date | January 2011 |
| Creators | Barnes, Samuel |
| Contributors | Neill, Joanna C. |
| Publisher | University of Bradford, School of Pharmacy |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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