Stimulation and destruction of the locus coeruleus: opposite effects on 3-methoxy-4-hydroxyphenylglycol sulfate levels in the rat cerebral cortex

The effect of electrical stimulation or electrothermic destruction of the locus coeruleus on cortical (including hippocampus) levels of 3-methoxy-4-hydroxyphenylglycol sulfate (MHPG-sulfate) was studied in rats. The locus coeruleus, which consists of norepinephrine (NE-containing nerve cell bodies, projects to the cerebral cortex and the hippocampus. 10 days after unilateral destruction of the locus coeruleus NE was decreased 78% and MHPG-sulfate, a central NE metabolite, was lowered by 69% in these areas. No alterations in levels of norepinephrine or MHPG-sulfate were observed on the contralateral side.Stimulation of the locus coeruleus induced a frequency-dependent increase in MHPG-sulfate. The most effective frequency was 20 pulses per sec. After 15 min of stimulation the MHPG-sulfate had reached a new steady state level of about 80% over the contralateral side.These findings indicate that MHPG-sulfate levels are dependent upon the integrity of NE neurons and that the level of rate of formation of MHPG-sulfate in the brain can be a reflection of the physiological activity of these neurons.