Norepinephrine regulation of cerebral glycogen utilization during seizures and ischemia.

Norepinephrine (NE) depletion of the cerebral cortex after lesion of the ipsilateral locus ceruleus (LC) causes abnormalities of cerebral oxidative metabolism when the cortex is stimulated to increased energy demand (Harik, S. I., J. C. LaManna, A. I. Light, and M. Rosenthal (1979) Science 206: 69-71; LaManna, J. C., S. I. Harik, A. I. Light, and M. Rosenthal (1981) Brain Res. 204: 87-101). These abnormalities were exhibited as decreased mitochondrial reducing equivalent flow. One possible cause of this would be the decreased availability of oxidative metabolic substrates in the NE-depleted cortex. We therefore investigated the effect of unilateral LC lesion and the resultant depletion of ipsilateral endogenous NE on glycogen and other energy metabolites in the cerebral cortex of rats under three conditions: (1) at "rest," (2) when energy demand is inncreased markedly by seizures, and (3) during total cerebral ischemia. We report no differences in cerebral metabolites between NE-depleted and control hemispheres at "rest." In seizures and ischemia, however, the increase in the level of adenosine 3':5'-monophosphate (cyclic AMP) and the breakdown of glycogen were impaired considerably in the NE-depleted cortex. The data suggest that depletion of central NE impairs cerebral glycogenolysis in response to increased energy demands and ischemia. Such impairment may be mediated via a cyclic AMP-related mechanism.