Abstract
The neurobiology of tobacco use is poorly understood, possibly in part because the relevant mechanisms might differ depending on past nicotine exposure and degree of addiction. In the present study we investigated whether these factors might affect the role of dopamine (DA). Using the acute phenylalanine/tyrosine depletion method (APTD), DA synthesis was transiently decreased in three groups of abstinent smokers (n=47): (1) early low-frequency smokers, who had smoked a maximum of five cigarettes per day for less than one year, (2) stable low-frequency smokers smoking at the same level as early low-frequency smokers for at least 3 years, and (3) stable high-frequency smokers, who smoked a minimum of 10 or more cigarettes per day for at least 5 years. Motivation to obtain tobacco was measured using a progressive ratio breakpoint schedule for nicotine-containing and de-nicotinized cigarettes. Compared with a nutritionally balanced control mixture, APTD decreased the self-administration of nicotine-containing cigarettes, and this occurred in all three groups of smokers. The results suggest that DA influenced the willingness to sustain effort for nicotine reward, and this was seen in participants at all three levels of cigarette addiction. In the transition from sporadic to addicted use, the role of DA in the motivation to seek drug may change less than previously proposed.
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Acknowledgements
We thank Franceen Lenoff and Kathleen Auclair for their excellent technical assistance.
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This work was funded by operating grants from CTCRI (017754) and CIHR (79919) to ML, and from NIH/NIDA (SNS-82249) and CIHR (DA022630 & RAN-79911) to LKF. JOL holds a Canada Research Chair in the Early Determinants of Adult Chronic Disease. KFC was the recipient of a scholarship from Fonds de la recherche en santé du Québec. CB and ML hold research chairs at McGill University. During the past 3 years, ML has received research funds from GSK for research unrelated to the present study. The remaining authors declare no conflict of interest.
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Venugopalan, V., Casey, K., O'Hara, C. et al. Acute Phenylalanine/Tyrosine Depletion Reduces Motivation to Smoke Cigarettes Across Stages of Addiction. Neuropsychopharmacol 36, 2469–2476 (2011). https://doi.org/10.1038/npp.2011.135
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DOI: https://doi.org/10.1038/npp.2011.135
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