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

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.

[1]  Roland E. Suri,et al.  TD models of reward predictive responses in dopamine neurons , 2002, Neural Networks.

[2]  A. Malhotra,et al.  Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[3]  E. Abercrombie,et al.  Differential Effect of Stress on In Vivo Dopamine Release in Striatum, Nucleus Accumbens, and Medial Frontal Cortex , 1989, Journal of neurochemistry.

[4]  A. Syrota,et al.  In Vivo Detection of Striatal Dopamine Release during Reward: A PET Study with [11C]Raclopride and a Single Dynamic Scan Approach , 2002, NeuroImage.

[5]  J. Day,et al.  Maternal care, hippocampal synaptogenesis and cognitive development in rats , 2000, Nature Neuroscience.

[6]  L. Tiedje,et al.  Pituitary-Adrenal and Autonomic Responses to Stress in Women After Sexual and Physical Abuse in Childhood , 2001 .

[7]  S. J. Gatley,et al.  Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects , 1997, Nature.

[8]  Karl J. Friston,et al.  A unified statistical approach for determining significant signals in images of cerebral activation , 1996, Human brain mapping.

[9]  P. Piazza,et al.  Higher and longer stress-induced increase in dopamine concentrations in the nucleus accumbens of animals predisposed to amphetamine self-administration. A microdialysis study , 1993, Brain Research.

[10]  A. Beck,et al.  An inventory for measuring depression. , 1961, Archives of general psychiatry.

[11]  R C Atkinson,et al.  Environmental regulation. , 1980, Science.

[12]  Jens C. Pruessner,et al.  Low self-esteem, induced failure and the adrenocortical stress response , 1999 .

[13]  F. Rougé-Pont,et al.  Individual differences in stress‐induced dopamine release in the nucleus accumbens are influenced by corticosterone , 1998, The European journal of neuroscience.

[14]  J. Salamone,et al.  Behavioral functions of nucleus accumbens dopamine: Empirical and conceptual problems with the anhedonia hypothesis , 1997, Neuroscience & Biobehavioral Reviews.

[15]  Hall Fs.  Social Deprivation of Neonatal, Adolescent, and Adult Rats Has Distinct Neurochemical and Behavioral Consequences , 1998 .

[16]  David S. Wishart,et al.  Clustan Graphics3 Interactive Graphics for Cluster Analysis , 1999 .

[17]  G. Parker,et al.  The parental bonding instrument , 1979, Social Psychiatry and Psychiatric Epidemiology.

[18]  K. Cho,et al.  Effects of corticosterone on excitatory amino acid responses in dopamine-sensitive neurons in the ventral tegmental area , 1999, Neuroscience.

[19]  A. Dagher,et al.  Amphetamine-Induced Increases in Extracellular Dopamine, Drug Wanting, and Novelty Seeking: A PET/[11C]Raclopride Study in Healthy Men , 2002, Neuropsychopharmacology.

[20]  F. Hall,et al.  Social deprivation of neonatal, adolescent, and adult rats has distinct neurochemical and behavioral consequences. , 1998, Critical reviews in neurobiology.

[21]  S. Ikemoto,et al.  The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking , 1999, Brain Research Reviews.

[22]  K. Worsley,et al.  A Statistical Method for the Analysis of Positron Emission Tomography Neuroreceptor Ligand Data , 2000, NeuroImage.

[23]  T. Robbins,et al.  Retarded acquisition and reduced expression of conditioned locomotor activity in adult rats following repeated early maternal separation: effects of prefeeding,d-amphetamine, dopamine antagonists and clonidine , 1996, Psychopharmacology.

[24]  P. Redgrave,et al.  Is the short-latency dopamine response too short to signal reward error? , 1999, Trends in Neurosciences.

[25]  L. Luecken.  Childhood Attachment and Loss Experiences Affect Adult Cardiovascular and Cortisol Function , 1998, Psychosomatic medicine.

[26]  C. Kirschbaum,et al.  Burnout, perceived stress, and cortisol responses to awakening. , 1999, Psychosomatic medicine.

[27]  B. Långström,et al.  Amphetamine effects on dopamine release and synthesis rate studied in the Rhesus monkey brain by positron emission tomography , 2005, Journal of Neural Transmission.

[28]  W C Eckelman,et al.  Kinetic Modeling of [11C]Raclopride: Combined PET-Microdialysis Studies , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[29]  C. Adler,et al.  Effects of Acute Metabolic Stress on Striatal Dopamine Release in Healthy Volunteers , 2000, Neuropsychopharmacology.

[30]  R. Wise,et al.  Brain dopamine and reward. , 1989, Annual review of psychology.

[31]  S. Haber,et al.  Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[32]  R. Bonsall,et al.  Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. , 2000, JAMA.

[33]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[34]  M. Laruelle.  Imaging Synaptic Neurotransmission with in Vivo Binding Competition Techniques: A Critical Review , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[35]  K. Berridge,et al.  What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? , 1998, Brain Research Reviews.

[36]  D. Bindra.  How adaptive behavior is produced: a perceptual-motivational alternative to response reinforcements , 1978, Behavioral and Brain Sciences.

[37]  Michael J Meaney,et al.  Environmental regulation of the development of mesolimbic dopamine systems: a neurobiological mechanism for vulnerability to drug abuse? , 2002, Psychoneuroendocrinology.

[38]  A. Lammertsma,et al.  Simplified Reference Tissue Model for PET Receptor Studies , 1996, NeuroImage.

[39]  D. Collins,et al.  Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space , 1994, Journal of computer assisted tomography.

[40]  C. Kirschbaum,et al.  Synthesis of a cortisol-biotin conjugate and evaluation as a tracer in an immunoassay for salivary cortisol measurement , 1992, The Journal of Steroid Biochemistry and Molecular Biology.

[41]  T. Robbins,et al.  Maternal deprivation of neonatal rats produces enduring changes in dopamine function , 1999, Synapse.

[42]  Shakti Sharma,et al.  Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Shakti Sharma,et al.  Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. , 1997, Science.

[44]  A. Dagher,et al.  Alcohol promotes dopamine release in the human nucleus accumbens , 2003, Synapse.

[45]  L. Eisenberg,et al.  Maternal deprivation. , 1956, Pediatrics.

[46]  Jeffrey E. Grice,et al.  Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change , 2004 .

[47]  Vincent J. Cunningham,et al.  Parametric Imaging of Ligand-Receptor Binding in PET Using a Simplified Reference Region Model , 1997, NeuroImage.

[48]  N. Volkow,et al.  Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects. , 1997, The American journal of psychiatry.

[49]  M. Marinelli,et al.  Interaction between glucocorticoid hormones, stress and psychostimulant drugs * , 2002, The European journal of neuroscience.

[50]  D. Brooks,et al.  Evidence for striatal dopamine release during a video game , 1998, Nature.

[51]  P B Hoffer,et al.  Microdialysis and SPECT measurements of amphetamine‐induced dopamine release in nonhuman primates , 1997, Synapse.

[52]  F. Rougé-Pont,et al.  Glucocorticoids have state-dependent stimulant effects on the mesencephalic dopaminergic transmission. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[53]  J S Fowler,et al.  Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[54]  P. Piazza,et al.  Dopaminergic activity is reduced in the prefrontal cortex and increased in the nucleus accumbens of rats predisposed to develop amphetamine self-administration , 1991, Brain Research.