Effect of Apomorphine on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow (with an Appendix on its Statistical Analysis)

Abstract

The alterations in local glucose utilization and local blood flow in 36 discrete regions of the central nervous system (CNS) that occur following the intravenous administration of the putative dopaminergic agonist, apomorphine (0.5 mg/kg), have been measured using the quantitative autoradiographic 14C-2-deoxyglucose and 14C-iodoantipyrine techniques. In eight of the regions examined (frontal and sensory-motor cortices, ventral thalamus, caudate nucleus, globus pallidus, substantia nigra, subthalamic nucleus, and posterior cerebellar hemisphere), significant elevations of local cerebral blood flow (CBF) were observed following apomorphine administration. In these eight regions, proportionately similar, significant elevations in local glucose utilization were observed following apomorphine. In two of the regions investigated (anterior cingulate cortex and lateral habenular nucleus), significant reductions in both local blood flow and glucose utilization were observed following apomorphine administration. In the majority of regions examined (26 of the total 36), apomorphine did not alter significantly either blood flow or glucose use. Using a statistical approach, described in detail in an appendix, the relationship between local rates of glucose utilization and local levels of tissue blood flow was analyzed. A relationship between local CBF and local glucose utilization was found following apomorphine, and the nature of this relationship was indistinguishable from that observed in control animals. In no region of the CNS was a significant deviation from the normal CBF–glucose use relationship demonstrated following apomorphine administration. These results point to the greater importance of the effects of apomorphine upon tissue metabolic activity, rather than its direct vascular action, as being the major mechanism underlying the observed alterations in local CBF. The statistical methods provide a rigorous analytical approach to the analysis of alterations in the relationship, both locally and globally, of blood supply to glucose utilization.