The effect of the dopamine agonist, apomorphine, on regional cerebral blood flow in normal volunteers

Apomorphine, a non-selective dopamine agonist, has been used as a pharmacological probe for investigating central dopaminergic neurotransmission in psychiatric illness. In this study repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers before, and after, the administration of apomorphine (5 or 10 micrograms/kg), or placebo. The difference in rCBF, before and after drug (apomorphine versus placebo), was used to identify brain areas affected by apomorphine. Compared to placebo, both doses of apomorphine increased blood flow in the anterior cingulate cortex. Apomorphine 10 micrograms/kg also increased prefrontal rCBF (right > left). No decreases in rCBF were noted following either dose of apomorphine. Apomorphine-induced increases of anterior cingulate blood flow might serve as an in vivo index of central dopamine function. Such an approach would complement established neuroendocrine challenge paradigms for investigating central dopamine neurotransmission in psychiatric illness.

[1]  M. Arné-Bès,et al.  Effects of a Dopaminergic Agonist (Piribedil) on Cerebral Blood Flow in Man , 1982, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  C. Nahmias,et al.  Apomorphine effects on brain metabolism in neuroleptic-naive schizophrenic patients , 1991, Psychiatry Research: Neuroimaging.

[3]  S. Checkley Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness , 1980, Psychological Medicine.

[4]  M. Posner,et al.  Localization of cognitive operations in the human brain. , 1988, Science.

[5]  Karl J. Friston,et al.  Localisation in PET Images: Direct Fitting of the Intercommissural (AC—PC) Line , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  J. Palacios,et al.  Dopamine receptors in human brain: Autoradiographic distribution of D1 sites , 1989, Neuroscience.

[7]  J. Mcculloch,et al.  Cerebral circulation: effect of stimulation and blockade of dopamine receptors. , 1977, The American journal of physiology.

[8]  Karl J. Friston,et al.  Plastic transformation of PET images. , 1991, Journal of computer assisted tomography.

[9]  Karl J. Friston,et al.  Comparing Functional (PET) Images: The Assessment of Significant Change , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  J. Mcculloch Mapping Functional Alterations in the CNS With [14C]Deoxyglucose , 1982 .

[11]  Karl J. Friston,et al.  The Relationship between Global and Local Changes in PET Scans , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[12]  S. Iversen,et al.  Handbook of Psychopharmacology , 1988, Springer US.

[13]  P M Bloomfield,et al.  Combination of Dynamic and Integral Methods for Generating Reproducible Functional CBF Images , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  H. Meltzer,et al.  Psychopharmacology : the third generation of progress , 1987 .

[15]  S. Checkley,et al.  Increased sensitivity of dopamine receptors and recurrence of affective psychosis after childbirth. , 1991, BMJ.

[16]  Karl J. Friston,et al.  Measuring the neuromodulatory effects of drugs in man with positron emission tomography , 1992, Neuroscience Letters.

[17]  F. Gerstenbrand,et al.  PET and NMR : new perspectives in neuroimaging and in clinical neurochemistry : proceedings of a symposium held in Padova, Italy, May 15-17, 1985 , 1986 .

[18]  T. Cox,et al.  An inventory for the measurement of self-reported stress and arousal. , 1978, The British journal of social and clinical psychology.

[19]  P. Cowen,et al.  ELECTROCONVULSIVE THERAPY AND THE BRAIN: EVIDENCE FOR INCREASED DOPAMINE-MEDIATED RESPONSES , 1982, The Lancet.

[20]  J. Palacios,et al.  Dopamine receptors in human brain: Autoradiographic distribution of D2 sites , 1989, Neuroscience.

[21]  David J. Hand,et al.  Multivariate Analysis Of Variance And Repeated Measures , 1987 .

[22]  J. Mcculloch,et al.  Effect of Apomorphine on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow (with an Appendix on its Statistical Analysis) , 1982, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  P. Dupui,et al.  Cerebral Blood Flow Studied by Xenon-133 Inhalation Technique in Parkinsonism: Loss of Hyperfrontal Pattern , 1983, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  J. Mcculloch,et al.  Vasomotor responses of cerebral arterioles in situ to putative dopamine receptor agonists , 1985, British journal of pharmacology.

[25]  R J Wise,et al.  The effects of L-DOPA on regional cerebral blood flow and oxygen metabolism in patients with Parkinson's disease. , 1985, Brain : a journal of neurology.

[26]  J. Mcculloch,et al.  Effects of dopaminergic agonists and antagonists on isolated cerebral blood vessels. , 1978, Acta physiologica Scandinavica.

[27]  O. Rascol,et al.  Subcutaneous apomorphine increases regional cerebral blood flow in parkinsonian patients via peripheral mechanisms. , 1991, British journal of clinical pharmacology.

[28]  B. Berger,et al.  Dopaminergic innervation of the cerebral cortex: unexpected differences between rodents and primates , 1991, Trends in Neurosciences.

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

[30]  J. Keyser,et al.  The mesoneocortical dopamine neuron system , 1990, Neurology.

[31]  J. Nutt,et al.  Peripheral pharmacokinetics of apomorphine in humans , 1989, Annals of neurology.

[32]  M. Mintun,et al.  Noninvasive functional brain mapping by change-distribution analysis of averaged PET images of H215O tissue activity. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[33]  M. Gilardi,et al.  Physical performance of the latest generation of commercial positron scanner , 1988 .

[34]  H. Meltzer,et al.  Growth hormone and prolactin response to apomorphine in schizophrenia and the major affective disorders. Relation to duration of illness and depressive symptoms. , 1984, Archives of general psychiatry.

[35]  D. Weinberger,et al.  The effect of apomorphine on regional cerebral blood flow in schizophrenia. , 1989, The Journal of neuropsychiatry and clinical neurosciences.

[36]  D. Loewenstein,et al.  Behavioral Activation and the Variability of Cerebral Glucose Metabolic Measurements , 1987, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[37]  T. Hökfelt,et al.  Evidence for dopamine receptor stimulation by apomorphine , 1967, The Journal of pharmacy and pharmacology.

[38]  N. Toda INFLUENCE OF DOPAMINE AND NORADRENALINE ON ISOLATED CEREBRAL ARTERIES OF THE DOG , 1976, British journal of pharmacology.