UC San Diego

Cognitive deficits are characteristic symptoms of schizophrenia, but remain largely untreated. Targeted Cognitive Training (TCT), a computerized training regimen designed to enhance spared function, is a putative new treatment for this symptom class. Mechanisms underlying the effects of TCT are unclear, however. This thesis describes three main studies (and one supplemental study) that aimed to develop and validate the Rat Sweep Discrimination Task (RSDT), a putative model of the Auditory Sweep Discrimination Task featured in human TCT. Nine different permutations of the basic RSDT were developed, each of which were intended to build rats’ association of auditory frequency “sweeps” with requisite response outputs. Rats were unable to reliably complete the RSDT without assistance from spatial cues. In order to probe the pharmacological predictive validity of the RSDT, we assessed the effects of d-amphetamine (d-AMPH, previously demonstrated to facilitate the effects of TCT in humans; 0.1, 0.25, 0.30 mg/kg, i.p.) on performance of the one version of the task in which rats were most competent (full spatial cues). No effect of d-AMPH was observed on any measure of the RSDT, which, taken together with rats’ overall poor performance in the majority of the RSDT versions developed, indicates that the RSDT requires further refinement before it can be applied as a model of human TCT. Possible limitations of the studies are discussed, and it is concluded that sub-optimal auditory stimulus specifications were the most likely cause of rats’ poor performance, and that small sample sizes likely prevented the detection of d-AMPH effects