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

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

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience Psychology, Behavioral Health Sciences, Mental Health
Mot-clé	DOPS Neill norepinephrine Aman 3CSRTT knockout ADHD Aman Ali mice DOPAMINE β-HYDROXYLASE DBH attention
Committee Chair / Thesis Advisor	Neill, Darryl B, Emory University
Committee Members	Frenzel, Kristen E, Emory University Phillips, Robert, Emory University

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