Date of Award

1-1-2009

Document Type

Campus Access Thesis

Department

Psychology

Sub-Department

Experimental Psychology

First Advisor

Charles F. Mactutus

Abstract

Sensorimotor gating, the process by which organisms filter extraneous sensory stimuli, is commonly assessed with manipulations of prepulse inhibition (PPI). Alterations in gating are observed in individuals with schizophrenia, HIV-1 dementia and other neuropsychiatric disorders. Dopaminergic pathways play a putative role in sensorimotor gating. It is well-established that apomorphine (APO), a dopamine agonist, disrupts PPI of the auditory startle response at low prepulse intensities (5-10 dB above baseline noise) at an interstimulus interval (ISI, time between the prepulse and the startle stimulus) of 100msec. In the present study, it was hypothesized that disruption of PPI by APO would also occur with a visual prepulse stimulus, and further, that a range of ISIs would provide a more precise index of any such disruption. It was also hypothesized that PPI of the auditory startle response would be disrupted by APO with a prepulse of a higher intensity (15 dB above baseline noise), when assessed with a range of ISIs. Accordingly, sensorimotor gating was measured with visual and auditory prepulse stimuli in the PPI paradigm (ISIs of 0, 8, 40, 80, 120, 4000 msec, 6 trial blocks, Latinsquare design). A within-subjects design was used for each experiment, with 12 adult male Sprague-Dawley rats that were tested 5 minutes after a subcutaneous injection of saline or one of three apomorphine (APO) doses (0.1, 0.25, and 0.5 mg/kg) in an ascending series with 48 hr between assessments. Auditory PPI with a low prepulse intensity of 75dB was disrupted by APO at the 100 msec ISI, as previous studies have shown. Auditory PPI with a high prepulse intensity of 85 dB was not significantly disrupted by APO at the 100 msec ISI, as found previously. However, the use of a range of ISIs revealed disruption of PPI by APO; in particular, there was a flattening of the ISI function with an increase in APO dose. The change in the function indicates an effect of APO on temporal sensorimotor gating. The ISI function for the visual PPI was also flattened with an increase in APO dose, which supports the notion of the generality of PPI disruption by APO across prepulse stimulus modalities.

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