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.

Download full-text


Available from: Alice Egerton
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Pathological gambling (PG) is a behavioural addiction associated with elevated impulsivity and suspected dopamine dysregulation. Reduced striatal dopamine D(2)/D(3) receptor availability has been reported in drug addiction, and may constitute a premorbid vulnerability marker for addictive disorders. The aim of the present study was to assess striatal dopamine D(2)/D(3) receptor availability in PG, and its association with trait impulsivity. Males with PG (n=9) and male healthy controls (n=9) underwent [11C]-raclopride positron emission tomography imaging and completed the UPPS-P impulsivity scale. There was no significant difference between groups in striatal dopamine D(2)/D(3) receptor availability, in contrast to previous reports in drug addiction. However, mood-related impulsivity ('Urgency') was negatively correlated with [11C]-raclopride binding potentials in the PG group. The absence of a group difference in striatal dopamine binding implies a distinction between behavioural addictions and drug addictions. Nevertheless, our data indicate heterogeneity in dopamine receptor availability in disordered gambling, such that individuals with high mood-related impulsivity may show differential benefits from dopamine-based medications.
    Full-text · Article · Jul 2012 · NeuroImage
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Positron emission tomography (PET) studies have reported an association between reduced striatal dopamine D2/3 receptor availability and higher scores on self-report measures of trait impulsivity in healthy adults. However, impulsivity is a multi-faceted construct, and it is unclear which aspect(s) of impulsivity might be driving these associations. The current study aimed to investigate the relationship between limbic (ventral) striatal D2/3 receptor availability and individual components of impulsivity (attentional, motor and non-planning) using the Barratt Impulsiveness Scale (BIS-11) and [(11)C]raclopride PET in 23 healthy volunteers. A partial correlational analysis showed a significant association between non-planning impulsiveness (lack of forethought or 'futuring') and limbic D2/3 receptor availability, which was only apparent after the exclusion of potential dissimulators (indexed by high scores on impression management). Our findings suggest that non-planning impulsiveness is associated with individual variation in limbic striatal D2/3 receptor availability and that different facets of impulsivity may have specific neurochemical correlates. Future studies that combine D2/3 receptor imaging with behavioral measures of impulsivity are required to further elucidate the precise relationship between individual components of trait impulsivity and brain dopaminergic function.
    Full-text · Article · May 2012 · Psychiatry Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous positron emission tomography (PET) studies have consistently shown a negative association between striatal D(2/3) receptor availability and socially desirable responding (SDR). However, as SDR is a complex personality trait, the functional significance of this relationship is unclear. The aim of the present study was to determine whether the relationship between D(2/3) receptor availability and SDR reflects a tendency to present oneself positively to others, consistent with social conformity (impression management, IM), or the tendency to view one's own behavior positively (self-deceptive enhancement, SDE). Striatal D(2/3) receptor availability was assessed in 23 healthy volunteers using [(11)C]raclopride PET. SDR was assessed using the Lie scale of the revised Eysenck Personality Questionnaire, and IM and SDE were measured using the Paulhus Deception Scales. Analysis of personality variables revealed a positive relationship between Lie and log IM (r=0.64, p=0.01) but not Lie and SDE (r=-0.36, ns). Consistent with previous findings, Lie was negatively associated with D(2/3) receptor availability in the sensorimotor striatum (r=- 0.55, p=0.05), and a similar trend-level relationship was observed for log IM (r=-0.54 p=0.06) but not SDE (r=0.23, ns). Whilst these associations are modest, results suggest that striatal D(2/3) receptor availability may be particularly associated with social conformity, rather than self-deception.
    No preview · Article · Nov 2010 · NeuroImage
Show more