Investigating the Effects of Chronic Amphetamine Treatment on the Midbrain Superior Colliculus

Turner, Amy (2018). Investigating the Effects of Chronic Amphetamine Treatment on the Midbrain Superior Colliculus. PhD thesis The Open University.



Heightened distractibility, the reduced ability to filter out irrelevant information, is a disruptive symptom found in numerous conditions and healthy ageing. It is most effectively treated with psychostimulant drugs, such as amphetamine, which are given chronically in attention deficit hyperactivity disorder (ADHD). There is converging evidence linking the superior colliculus (SC) to the regulation of distractibility, and acute amphetamine administration is known to suppress collicular responsiveness, however relatively little is known about its mechanism of action and long lasting effects when administered chronically. It is therefore the aim of this thesis to investigate the effects of chronic treatment with amphetamine on the SC, as a neural correlate of distractibility. To achieve this, adolescent Hooded Lister rats were treated orally with amphetamine (2, 5 or 10 mg/kg) or a control (vehicle or untreated) for one month. The effects of treatment were then explored by investigating: collicular-dependant and locomotor behaviour; visual responsiveness of the superficial SC; responses to an acute amphetamine challenge; and the morphology of the superficial SC.

At high doses, oral amphetamine treatment resulted in the development of locomotor tolerance, in contrast to previous research using i.p. administration which report sensitisation. Evidence of suppression of activity in the SC was identified from a reduced ability to perform collicular dependant behaviours, and from weaker light responsiveness measured from multi-unit activity in the superficial SC following treatment with high doses of amphetamine. Evidence was also found of a potential compensatory mechanism involving synaptophysin expression and enhanced peri-synaptic activity. This thesis also investigated the types of dendritic spines prevalent in the superficial SC for the first time, and found that these structures were unaffected by amphetamine treatment. These results indicate that the therapeutic effects of amphetamine may stem from suppression of collicular activity, and the SC is susceptible to amphetamine induced remodelling.

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