Inflow of oxygen and glucose into brain tissue induced by intravenous norepinephrine: relationships with central metabolic and peripheral vascular responses

As an essential part of sympathetic activation that prepares the organism for "fight or flight," peripheral norepinephrine (NE) plays an important role in regulating cardiac activity and the tone of blood vessels, increasing blood flow to the heart and the brain and decreasing blood flow to the organs not as necessary for immediate survival. To assess whether this effect is applicable to the brain, we used high-speed amperometry to measure the changes in nucleus accumbens (NAc) levels of oxygen and glucose induced by intravenous (iv) injections of NE in awake, freely-moving rats. We found that NE at low doses (2-18 –g/kg) induces correlative increases in NAc oxygen and glucose, suggesting local vasodilation and enhanced entry of these substances into brain tissue from the arterial blood. By using temperature recordings from the NAc, temporal muscle, and skin, we show that this central effect is associated with strong skin vasoconstriction and phasic increases in intra-brain heat production, indicative of metabolic neural activation. A tight, direct correlation between NE-induced changes in metabolic activity and NAc levels of oxygen and glucose levels suggests that local cerebral vasodilation is triggered via a neuro-vascular coupling mechanism. Our data suggest that NE, by changing vascular tone and cardiac activity, triggers a visceral sensory signal that rapidly reaches the CNS via sensory nerves and induces neural activation. This neural activation leads to a chain of neuro-vascular events that promote entry of oxygen and glucose into brain tissue, thus preventing any possible metabolic deficit during functional activation.

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