Characterisation of the Superior Colliculus in a Rat Model of Attention Deficit/Hyperactivity Disorder

Brace, Louise Rose (2015). Characterisation of the Superior Colliculus in a Rat Model of Attention Deficit/Hyperactivity Disorder. PhD thesis The Open University.



Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioural disorder of childhood onset. Core symptoms include hyperactivity, impulsivity and inattention. Despite high prevalence and effective pharmacological treatment, the pathophysiology is poorly understood. Present theories of the etiology of ADHD suggest a crucial influence of dopamine. To date, little investigation has focussed on structures upstream of dopamine neurons which could cause these abnormalities. The midbrain superior colliculus (SC) is conserved across species and plays a role in saccade generation, visual saliency and attention. Evidence suggests that the SC could be dysfunctional in ADHD, and may explain core symptoms of ADHD, providing a site for action of therapeutic treatments. The spontaneous hypertensive rat (SHR), an animal model for ADHD has shown face validity, construct validity and predictive validity, and is the most commonly used animal model of ADHD. Understanding the etiology of the ADHD-like behaviours in the SHR is important in improving our understanding of the etiology of ADHD itself. This thesis presents work that demonstrates that the SHR responds to visual and auditory stimuli in a different way behaviourally and physiologically compared to two control strains, with these differences likely to be mediated by alterations within and upstream of the SC, respectively, resulting in altered saliency of sensory stimuli. These results are compatible with the two unifying theories of ADHD, but suggest that the dysregulation of dopamine is secondary to changes upstream in the SC and structures projecting to it. The findings of slower onset latency in the SHR are also in line with ADHD and the ADHD-like behaviours seen in the SHR and support ADHD being a development disorder. ADHD treatments such as amphetamine and fluoxetine may have a mechanism of action within the SC, and therefore normalise the exaggerated response, yet the results from the current experiment on drug effects are inconclusive.

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