Atomoxetine produces changes in cortico-basal thalamic loop circuits: Assessed by phMRI BOLD contrast

Abstract

Atomoxetine is a selective noradrenaline reuptake inhibitor used in the treatment of attention deficit hyperactivity disorder (ADHD) which has not yet been assessed using pharmacological neuroimaging for its effects on rat brain activity. The pharmacological magnetic resonance imaging (phMRI) blood oxygenation level dependent (BOLD) response was determined in rat brain regions following administration of atomoxetine. Rats were individually placed into a 2.35T Bruker magnet for 60 min to achieve basal recording of changes in signal intensity. Either saline ( n = 9) or atomoxetine hydrochloride (2 mg/kg; i.p.; n = 10) was then administered and recording continued for a further 90 min. Data were analysed for BOLD random effects using statistical parametric maps and time course analysis. The main changes observed were widespread negative BOLD responses in the caudate putamen and changes in brain regions associated with the cortico-basal thalamic loop circuits. BOLD changes in the basal ganglia help explain its efficacy in reducing hyperactivity observed in ADHD patients. Although positive BOLD changes in the prefrontal cortex were limited to the ventral orbital cortex this is an area associated with behavioral control and may be of relevance to the use of the drug in ADHD.