To date, research using rodent models has primarily dealt with the visual aspects of attention, while in the present research, we examined neurochemical modulation of attentional processes using both a visual and an olfactory five choice serial reaction time task (5-CSRTT). The nucleus basalis magnocellularis (NBM) in the basal forebrain is the primary source of cortical cholinergic input, which is thought to have an important modulatory effect on rat attentional processes. Thus, after successful acquisition of the task, the rats were subjected to either a cholinergic immunotoxic or sham lesion surgery of the NBM. Cortical cholinergic deafferentation of the cortical mantle was induced by bilaterally infusing 0.2 µg/µl of the cholinergic immunotoxin, 192 IgG-saporin, into the NBM (saporin-lesion). Reduction of cortical cholinergic modulation led to comparable attentional impairments in the saporin-lesion group, relative to the sham-lesioned group, on both visual and olfactory versions of the 5-CSRTT.

To date, research using rodent models has primarily dealt with the visual aspects of attention, while in the present research, we examined neurochemical modulation of attentional processes using both a visual and an olfactory five choice serial reaction time task (5-CSRTT). The nucleus basalis magnocellularis (NBM) in the basal forebrain is the primary source of cortical cholinergic input, which is thought to have an important modulatory effect on rat attentional processes. Thus, after successful acquisition of the task, the rats were subjected to either a cholinergic immunotoxic or sham lesion surgery of the NBM. Cortical cholinergic deafferentation of the cortical mantle was induced by bilaterally infusing 0.2 µg/µl of the cholinergic immunotoxin, 192 IgG-saporin, into the NBM (saporin-lesion). Reduction of cortical cholinergic modulation led to comparable attentional impairments in the saporin-lesion group, relative to the sham-lesioned group, on both visual and olfactory versions of the 5-CSRTT.

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.

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.