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The Journal of Neuroscience, March 17, 2004, 24(11):2825-2831; doi:10.1523/JNEUROSCI.3422-03.2004

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Behavioral/Systems/Cognitive
Dopamine Release in Response to a Psychological Stress in Humans and Its Relationship to Early Life Maternal Care: A Positron Emission Tomography Study Using [¹¹C]Raclopride

Jens C. Pruessner,^1,2 Frances Champagne,² Michael J. Meaney,² and Alain Dagher¹

¹McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Canada H3A 2B4, and ²Douglas Hospital Research Center, Montreal, Canada H4H 1R3

Mesolimbic dopamine is thought to play a role in the processing of rewards. However, animal studies also demonstrate dopamine release in response to aversive stressful stimuli. Also, in animal studies, disruptions of the mother–infant relationship have been shown to have long-lasting effects on the mesolimbic dopamine system and the hypothalamic-pituitary adrenal axis. We therefore investigated dopamine release in response to stress in human subjects, considering the relationship to early life parental care. We screened 120 healthy young college students for parental care in early life using a combination of telephone interviews and questionnaires. Five students from the top end and five students from the bottom end of the parental care distribution were then invited for a positron emission tomography study using [¹¹C]raclopride and a psychosocial stress task. The psychosocial stressor caused a significant release of dopamine in the ventral striatum as indicated by a reduction in [¹¹C]raclopride binding potential in the stress versus resting condition in subjects reporting low parental care. Moreover, the magnitude of the salivary cortisol response to stress was significantly correlated with the reduction in [¹¹C]raclopride binding in the ventral striatum (r = 0.78), consistent with a facilitating effect of cortisol on dopamine neuron firing. These data suggest that aversive stressful events can be associated with mesolimbic dopamine release in humans, and that the method presented here may be useful to study the effects of early life events on neurobiological stress systems.

Key words: stress; dopamine; [¹¹C]raclopride; nucleus accumbens; cortisol; maternal care

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Received July 21, 2003; revised January 30, 2004; accepted January 31, 2004.

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