Effects of alcohol or stress, or their combination, on prepulse inhibiton in mice selectively bred for high- and low-alcohol preference

Matthew S Powers, Purdue University

Abstract

Evidence suggests that alcoholism is heritable and can be influenced by many environmental factors. Stress is one such factor that has long been thought to predispose individuals to the development of alcoholism. Although much research has focused on how stress and inherited risk interact to influence the development of alcoholism, the mechanisms remain unclear. One popular theory is that alcohol reduces the psychological and physiological consequences of stress. Prepulse inhibition (PPI) of the acoustic startle response (ASR), a form of sensorimotor gating, is one measure that is influenced by genetics, alcohol and stress exposure, and therefore may be a useful tool to explore the relationship between these factors. The purpose of this thesis was to examine the relationship between alcohol, stress, and their combination on PPI in an animal model of alcoholism, selectively bred high- (HAP) and low- (LAP) alcohol preferring mice. Experiment 1 tested the hypothesis that acute alcohol treatment would disrupt PPI in HAP mice and have no effect in LAP mice. This hypothesis is based on evidence that alcohol disrupts PPI in high alcohol preferring P rats but not in their low alcohol preferring counterparts. The results from experiment 1 did not support this hypothesis in that acute alcohol exposure significantly increased PPI and startle responding in HAP male mice while having no effect in LAP mice of either sex. Experiment 2 tested the hypothesis that repeated restraint stress would disrupt PPI independent of selected line, but HAP mice would be more sensitive to the disrupting effect. Stress did not affect PPI in either line or sex, but stress significantly reduced startle responding in LAP male mice only. This study also examined the effect of acute alcohol following repeated stress exposure. It was hypothesized that alcohol treatment following stress exposure would blunt the effect that stress has on PPI in HAP mice only, because only HAP mice should be sensitive to the effect of alcohol on PPI. This prediction is based on the popular theory that alcohol relieves the psychological and physiological consequences of stress. Although alcohol did not significantly increase PPI in Experiment 2, the pattern of responding was similar to Experiment 1 in that alcohol increased PPI. In conclusion, the data from Experiment 1 suggest that alcohol may have beneficial effects on sensorimotor gating in males with an increased likelihood to develop alcoholism. The findings from Experiment 2 suggest that a predisposition for alcoholism does not seem to be related to an increased sensitivity to repeated stress exposure, as measured by PPI. More work is needed to assess the time course of stress effects on PPI as well as to explore how exogenous administration of stress-related hormones influence responding in HAP and LAP mice. Future work should also focus on the mechanism of increased PPI following acute alcohol exposure in HAP mice by pharmacologically manipulating both the GABAergic and dopaminergic systems, as both of these neurochemical systems have been implicated in the modulation of PPI.

Degree

M.S.

Advisors

Chester, Purdue University.

Subject Area

Behavioral Sciences

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