Acute effect of the anti-addiction drug bupropion on extracellular dopamine concentrations in the human striatum: An [11C]raclopride PET study

Psychiatric Imaging, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
NeuroImage (Impact Factor: 6.36). 12/2009; 50(1):260-6. DOI: 10.1016/j.neuroimage.2009.11.077
Source: PubMed


Bupropion is an effective medication in treating addiction and is widely used as an aid to smoking cessation. Bupropion inhibits striatal dopamine reuptake via dopamine transporter blockade, but it is unknown whether this leads to increased extracellular dopamine levels at clinical doses in man. The effects of bupropion on extracellular dopamine levels in the striatum were investigated using [(11)C]raclopride positron emission tomography (PET) imaging in rats administered saline, 11 or 25 mg/kg bupropion i.p. and in healthy human volunteers administered either placebo or 150 mg bupropion (Zyban Sustained-Release). A cognitive task was used to stimulate dopamine release in the human study. In rats, bupropion significantly decreased [(11)C]raclopride specific binding in the striatum, consistent with increases in extracellular dopamine concentrations. In man, no significant decreases in striatal [(11)C]raclopride specific binding were observed. Levels of dopamine transporter occupancy in the rat at 11 and 25 mg/kg bupropion i.p. were higher than predicted to occur in man at the dose used. Thus, these data indicate that, at the low levels of dopamine transporter occupancy achieved in man at clinical doses, bupropion does not increase extracellular dopamine levels. These findings have important implications for understanding the mechanism of action underlying bupropions' therapeutic efficacy and for the development of novel treatments for addiction and depression.

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    • "A tenth PG subject was recruited but not available for analysis due to radiochemistry failure. Control volunteer baseline scans were identified from two previous studies (Egerton et al., 2010; Stokes et al., 2010) using a normative database of raclopride scans held at the MRC Clinical Sciences Centre, and did not differ from the PG group in age (t 16 = 0.53, p = .602). The PG participants were educated to at least high-school level with IQ estimates in the healthy range (Wechsler Adult Scale for Intelligence: mean 116, sd 10.8; National Adult Reading Test: mean 117, sd 5.7); past work indicates no consistent relationship between intelligence and dopamine binding levels. "
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    • "Statistical analysis was performed using Statistical Package for Social Sciences, SPSS, version 16.0 (SPSS Inc., Chicago, IL, USA). Due to the slight differences in [ 11 C]raclopride scanning protocol [(Lappin et al., 2009) versus (Lappin et al., 2009; Stokes et al., 2009; Egerton et al., 2010c)], an independent samples t-test was used to confirm that regional [ 11 C]raclopride BP ND did not vary significantly according to the study from which baseline [ 11 C]raclopride scans were collected . Hypothesis-led relationships between limbic striatal [ 11 C]raclopride BP ND bilaterally and the three second-order factors of the BIS (attention, motor and non-planning impulsiveness) were determined using partial bivariate correlation analyses, controlling for potentially confounding effects of [ 11 C]raclopride K bol which differed between the studies from which subjects were drawn, and age. "
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