Striatal and extrastriatal dopamine transporter in cannabis and tobacco addiction: a high-resolution PET study

Authors

  • Claire Leroy,

    Corresponding author
    1. INSERM U1000 Research Unit ‘Neuroimaging & Psychiatry’, IFR49, Orsay, France
    2. Maison de Solenn, Paris, France
    3. CEA, Service Hospitalier Frédéric Joliot, Orsay, France
    4. University Paris Sud, France
    5. University Paris Descartes, France
      Claire Leroy, CEA-INSERM U1000, I2BM, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay cedex, France. E-mail: claire.leroy@cea.fr
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  • Laurent Karila,

    1. Service d'Addictologie, Hôpital Paul Brousse, AP-HP, Villejuif, France
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  • Jean-Luc Martinot,

    1. INSERM U1000 Research Unit ‘Neuroimaging & Psychiatry’, IFR49, Orsay, France
    2. Maison de Solenn, Paris, France
    3. CEA, Service Hospitalier Frédéric Joliot, Orsay, France
    4. University Paris Sud, France
    5. University Paris Descartes, France
    6. CEA, Neurospin, Saclay, France
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  • Michaël Lukasiewicz,

    1. Service d'Addictologie, Hôpital Paul Brousse, AP-HP, Villejuif, France
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  • Edouard Duchesnay,

    1. INSERM U1000 Research Unit ‘Neuroimaging & Psychiatry’, IFR49, Orsay, France
    2. Maison de Solenn, Paris, France
    3. University Paris Sud, France
    4. University Paris Descartes, France
    5. CEA, Neurospin, Saclay, France
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  • Claude Comtat,

    1. CEA, Service Hospitalier Frédéric Joliot, Orsay, France
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  • Frédéric Dollé,

    1. CEA, Service Hospitalier Frédéric Joliot, Orsay, France
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  • Amine Benyamina,

    1. Service d'Addictologie, Hôpital Paul Brousse, AP-HP, Villejuif, France
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  • Eric Artiges,

    1. INSERM U1000 Research Unit ‘Neuroimaging & Psychiatry’, IFR49, Orsay, France
    2. Maison de Solenn, Paris, France
    3. CEA, Service Hospitalier Frédéric Joliot, Orsay, France
    4. University Paris Sud, France
    5. University Paris Descartes, France
    6. CEA, Neurospin, Saclay, France
    7. Service de Psychiatrie, Centre Hospitalier d'Orsay, France
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  • Maria-Joao Ribeiro,

    1. INSERM U1000 Research Unit ‘Neuroimaging & Psychiatry’, IFR49, Orsay, France
    2. Maison de Solenn, Paris, France
    3. CEA, Service Hospitalier Frédéric Joliot, Orsay, France
    4. University Paris Sud, France
    5. University Paris Descartes, France
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  • Michel Reynaud,

    1. Service d'Addictologie, Hôpital Paul Brousse, AP-HP, Villejuif, France
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    • Both authors contributed equally to this work.

  • Christian Trichard

    1. INSERM U1000 Research Unit ‘Neuroimaging & Psychiatry’, IFR49, Orsay, France
    2. Maison de Solenn, Paris, France
    3. CEA, Service Hospitalier Frédéric Joliot, Orsay, France
    4. University Paris Sud, France
    5. University Paris Descartes, France
    6. Service de Psychiatrie, Centre Hospitalier d'Orsay, France
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    • Both authors contributed equally to this work.


Claire Leroy, CEA-INSERM U1000, I2BM, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay cedex, France. E-mail: claire.leroy@cea.fr

ABSTRACT

The dopamine (DA) system is known to be involved in the reward and dependence mechanisms of addiction. However, modifications in dopaminergic neurotransmission associated with long-term tobacco and cannabis use have been poorly documented in vivo. In order to assess striatal and extrastriatal dopamine transporter (DAT) availability in tobacco and cannabis addiction, three groups of male age-matched subjects were compared: 11 healthy non-smoker subjects, 14 tobacco-dependent smokers (17.6 ± 5.3 cigarettes/day for 12.1 ± 8.5 years) and 13 cannabis and tobacco smokers (CTS) (4.8 ± 5.3 cannabis joints/day for 8.7 ± 3.9 years). DAT availability was examined in positron emission tomography (HRRT) with a high resolution research tomograph after injection of [11C]PE2I, a selective DAT radioligand. Region of interest and voxel-by-voxel approaches using a simplified reference tissue model were performed for the between-group comparison of DAT availability. Measurements in the dorsal striatum from both analyses were concordant and showed a mean 20% lower DAT availability in drug users compared with controls. Whole-brain analysis also revealed lower DAT availability in the ventral striatum, the midbrain, the middle cingulate and the thalamus (ranging from −15 to −30%). The DAT availability was slightly lower in all regions in CTS than in subjects who smoke tobacco only, but the difference does not reach a significant level. These results support the existence of a decrease in DAT availability associated with tobacco and cannabis addictions involving all dopaminergic brain circuits. These findings are consistent with the idea of a global decrease in cerebral DA activity in dependent subjects.

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