Dopaminergic dysfunction in abstinent dexamphetamine users: Results from a pharmacological fMRI study using a reward anticipation task and a methylphenidate challenge

Background: Dopamine (DA) is involved in systems governing motor actions, motivational processes and cognitive functions. Preclinical studies have shown that even relatively low doses of d-amphetamine (dAMPH) (equivalent to doses used in clinical Practice) can lead to DA neurotoxicity in rodents and non-human primates (Ricaurte et al., 2005). Methods: Therefore, we investigated the DAergic function in eight male recreational users of dAMPH and eight male healthy controls using functional magnetic resonance imaging (fMRI). We compared brain activation between both groups during a monetary incentive delay task (Knutson et al., 2001) with and without an oral methylphenidate (MPH) challenge. All subjects were abstinent for at least 2 weeks during the baseline scan. The second scan was performed on the same day 1.5. h after receiving an oral dose of 35. mg MPH (approximately 0.5. mg/kg) when peak MPH binding was assumed. Results: When anticipating reward, dAMPH users showed lower striatal activation in comparison to control subjects. In addition, MPH induced a reduction in the striatal activation during reward anticipation in healthy controls, whereas no such effect was observed in dAMPH users. Conculsion: The combination of these findings provides further evidence for frontostriatal DAergic dysfunction in recreational dAMPH users and is consistent with preclinical data suggesting neurotoxic effects of chronic dAMPH use. The findings of this explorative study could have important implications for humans in need for treatment with dAMPH, such as patients suffering from ADHD and therefore this study needs replication in a larger sample.