Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers

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2016
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Booij, Linda
Welfeld, Krzysztof
Leyton, Marco
Dagher, Alain
Boileau, Isabelle
Sibon, Igor
Baker, Glen B.
Diksic, Mirko
Benkelfat, Chawki
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Translational Psychiatry. 2016, 6(2), e740. eISSN 2158-3188. Available under: doi: 10.1038/tp.2016.6
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Dysregulation of the stress response system is a potential etiological factor in the development of and relapse to multiple neuropsychiatric disorders. Previously we reported that repeated intermittent d-amphetamine administration can lead to progressively greater dopamine release, thereby providing evidence of drug-induced neurochemical sensitization. Here, we test the hypothesis that repeated exposure to d-amphetamine increases dopaminergic responses to stress; that is, produces cross-sensitization. Using positron emission tomography, we measured in 17 healthy male volunteers (mean ± s.d. = 22.1 ± 3.4 years) [(11)C]raclopride binding responses to a validated psychosocial stress task before and 2 weeks after a regimen of repeated d-amphetamine (3 × 0.3 mg kg(-1), by mouth; n = 8) or placebo (3 × lactose, by mouth; n = 9). Mood and physiological measurements were recorded throughout each session. Before the d-amphetamine regimen, exposure to the stress task increased behavioral and physiological indices of stress (anxiety, heart rate, cortisol, all P ⩽ 0.05). Following the d-amphetamine regimen, the stress-induced cortisol responses were augmented (P < 0.04), and voxel-based analyses showed larger stress-induced decreases in [(11)C]raclopride non-displaceable binding potential across the striatum. In the placebo group, re-exposure to stress led to smaller clusters of decreased [(11)C]raclopride binding, primarily in the sensorimotor striatum (P < 0.05). Together, this study provides evidence for drug × stress cross-sensitization; moreover, random exposure to stimulants and/or stress cumulatively, while enhancing dopamine release in striatal areas, may contribute to a lowered set point for psychopathologies in which altered dopamine neurotransmission is invoked.

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ISO 690BOOIJ, Linda, Krzysztof WELFELD, Marco LEYTON, Alain DAGHER, Isabelle BOILEAU, Igor SIBON, Glen B. BAKER, Mirko DIKSIC, Jens C. PRUESSNER, Chawki BENKELFAT, 2016. Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers. In: Translational Psychiatry. 2016, 6(2), e740. eISSN 2158-3188. Available under: doi: 10.1038/tp.2016.6
BibTex
@article{Booij2016Dopam-38207,
  year={2016},
  doi={10.1038/tp.2016.6},
  title={Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers},
  number={2},
  volume={6},
  journal={Translational Psychiatry},
  author={Booij, Linda and Welfeld, Krzysztof and Leyton, Marco and Dagher, Alain and Boileau, Isabelle and Sibon, Igor and Baker, Glen B. and Diksic, Mirko and Pruessner, Jens C. and Benkelfat, Chawki},
  note={Article Number: e740}
}
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