Origin of free 3-methoxy-4-hydroxyphenylethyleneglycol in rat cerebrospinal fluid

Summary The origin of free 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG, a major metabolite of norepinephrine) in rat cerebrospinal fluid (CSF) was investigated using brain and spinal cord perfusions with artificial CSF, electrical stimulation of the locus coeruleus (LC) and the technique of retrograde cell labelling with horseradish peroxidase (HRP). The rates of appearance of MHPG into ventricular-cisternal and lumbar-cisternal perfusates were about 12.4 and 19.2 ng/hour respectively. Probenecid (200 mg/kg i.p.) did not alter the MHPG output in either preparation. Intravenous administration of 3µg MHPG did not substantially enhance the outflow of the metabolite in the ventricular-cisternal perfusate, indicating that MHPG found in the perfusate is of central origin. Maximal activation of central norepinephrine (NE)-containing neurons of the LC by electrical stimulation induced a 50% increase of MHPG levels in the ventricular-cisternal perfusate. In addition HRP was found to be retrogradely transported from the lateral ventricle to these LC-neurons.