AN INVESTIGATION OF ATTENTION IN DOPAMINE β-HYDROXYLASE KNOCKOUT MICE 公开

Ali, Aman Barkat (2010)

Permanent URL: https://etd.library.emory.edu/concern/etds/bn9997277?locale=zh
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Abstract

Abstract
An Investigation of Attention in Dopamine β-Hydroxylase Knockout Mice
By Aman Barkat Ali

The aim of this research was to test the hypothesis that norepinephrine signaling is critical for attention tasks in mice. To do this we used homozygous (DBH -/-) norepinephrine knockout mice and heterozygous (DBH +/-) mice and predict that the KO mice will perform lower on an attention test when compared to heterozygous (DBH +/-) mice, which are capable of synthesizing norepinephrine. Seven DBH -/- and seven DBH +/- mice were trained to nose poke on a Fixed-Ratio 1 (FR1) schedule for a palatable food reward without food deprivation. Twelve mice (6 of each genotype) were subsequently tested on the 3CSRTT test of attention. The results showed that DBH -/- mice, compared to the DBH +/- controls, were greatly impaired in 3CSRTT performance. Their poor performance was primarily manifested as more errors of omission. Only 2 of 6 DBH -/- mice learned the 3CSRTT with a 32 sec stimulus duration; while 5 of 6 DBH +/- controls learned the task. In tests at successively shorter stimulus durations (16, 8, 4, 2 sec), significantly more DBH +/- mice met criterion (less than 60% errors of omission and more than 80% correct responses) than DBH -/- mice. The poor performance of the DBH -/- mice was not due to an inability to nose poke, an inability to detect the light stimulus, or lower motivation to respond. Preliminary evidence showed that transient restoration of brain norepinephrine in the DBH -/- mice via DOPS administration tended to reverse their performance deficit. These data are consistent with a powerful role of norepinephrine in attention, and may be suggestive of a role of norepinephrine in Attention Deficit Disorder in humans.

Table of Contents

TABLE OF CONTENTS
INTRODUCTION...1
METHODS...5
PREDICTED EXPERIMENTAL OUTCOMES...15
RESULTS...16
DISCUSSION...33
FUTURE DIRECTIONS...38
REFERENCES...39

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