U161832.pdf (27 MB)
Measurement of cerebral activity in response to Dopaminergic drugs : studies using functional magnetic resonance imaging in the rat
thesisposted on 2014-12-15, 10:46 authored by Aisling L. Dixon
Dopamine is involved with many aspects of normal brain function, such as movement, emotion and motivation and its dysregulation is associated with diseases, such as schizophrenia and Parkinson's disease. Drug treatments for these conditions may cause side effects, hence, it is important to understand their mechanisms. Amphetamine administration is a popular model for studying reward, schizophrenia and behaviour. I modified this model to investigate changes in functional dopaminergic activity in the whole rat brain using Pharmacological magnetic resonance imaging (PhMRI). Halothane proved to be suitable anaesthetic for these experiments because it did not affect stimulated dopamine release unlike a-choralose.;Acute amphetamine challenge caused widespread increases in blood-oxygenation-level-dependent (BOLD) signal intensity in many subcortical dopaminergic structures, with a rim of negative BOLD observed in the cortex. Amphetamine acts by blocking reuptake of dopamine leading to activation of all dopamine receptor subtypes. To tease apart the mechanisms of the amphetamine response, I pretreated rats with specific antagonists prior to amphetamine. This had contrasting effects on the BOLD signal. D1 antagonist blocked most of the positive BOLD response to amphetamine whereas the D2 antagonist predominantly blocked and negative BOLD response. The acute effects of selective D1 and D2 agonists and antagonists on the BOLD response were observed in subcortical dopaminergic structures, largely corresponding with stimulation or blockade of the specific receptors types.;My experiments show that the recently-developed phMRI technique can be used to dissect the mechanisms of drug action in the whole brain.
Date of award2002-01-01
Awarding institutionUniversity of Leicester