Activation of specific cortical regions by apomorphine: an [15O]H2O PET study in humans

The purpose of this study was to investigate the functional effects of apomorphine, a non-selective dopamine agonist, on regional neuronal activity using regional cerebral blood flow, measured using [15O]H2O and positron emission tomography (PET), as an index. Eight normal volunteers were scanned twice before and twice after receiving 10 micrograms/kg subcutaneous apomorphine. Apomorphine produced the expected side-effects and endocrine response. Analysis of the PET scans revealed that apomorphine increased regional cerebral blood flow (rCBF), presumably reflecting a change in neuronal activity, in the anterior cingulate, ventral motor cortex and the dorsolateral prefrontal cortex along with a decrease in rCBF in the retrosplenial cingulate region. These regions form a functional network of brain regions modulated by the dopaminergic system.

[1]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

[2]  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.

[3]  D. Lewis.  The catecholaminergic innervation of primate prefrontal cortex. , 1992, Journal of neural transmission. Supplementum.

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

[5]  S. Lal.  Apomorphine in the evaluation of dopaminergic function in man , 1988, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[6]  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.

[7]  B. Berger,et al.  Catecholamine innervation of the human cerebral cortex as revealed by comparative immunohistochemistry of tyrosine hydroxylase and dopamine‐beta‐hydroxylase , 1989, The Journal of comparative neurology.

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

[9]  Karl J. Friston,et al.  The effect of the dopamine agonist, apomorphine, on regional cerebral blood flow in normal volunteers , 1993, Psychological Medicine.

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

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

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

[13]  J. Mcculloch,et al.  Effects of apomorphine upon local cerebral blood flow. , 1979, European journal of pharmacology.

[14]  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.

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

[16]  C R Olson,et al.  Topographic organization of cortical and subcortical projections to posterior cingulate cortex in the cat: Evidence for somatic, ocular, and complex subregions , 1992, The Journal of comparative neurology.

[17]  P. Strange.  Dopamine receptors in the basal ganglia: Relevance to parkinson's disease , 1993, Movement disorders : official journal of the Movement Disorder Society.

[18]  S. Kapur,et al.  Role of the dopaminergic system in depression , 1992, Biological Psychiatry.

[19]  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.