Brain 3,4-dihydroxyphenylethyleneglycol levels are dependent on central noradrenergic neuron activity

The effect of manipulations aimed to alter brain noradrenergic neuron activity on the levels of free and conjugated DOPEG in discrete brain areas was studied in the rat. Electrical stimulation of the medial forebrain bundle for 10-20 min produced a frequency dependent elevation of free and conjugated DOPEG concentrations in the anterior cerebral cortex and in the hippocampus. In contrast, acute interruption of noradrenergic nerve impulse flow by application of tetrodotoxin (50-100 ng) into the medial forebrain bundle markedly diminished cortical and hippocampal DOPEG levels at 0.5-2 h post-injection. Cortical conjugated and free DOPEG levels were also reduced (by 80-96%) 2-3 weeks after bilateral electrolytic lesion of the locus coeruleus, 6-hydroxydopamine-induced lesion of the ascending noradrenergic pathways or noradrenergic denervation by the neurotoxic agent DSP4. Finally, the alpha-adrenoceptor blocking agents yohimbine (1-10 mg/kg, ip) and RX 781094 (3-10 mg/kg, ip) increased whereas the alpha-adrenergic agonist clonidine (0.01-1 mg/kg, sc) decreased DOPEG levels in the cerebral cortex, hypothalamus and septal areas. These data indicate that free and conjugated DOPEG formation is dependent on, and may serve as an index of, central noradrenergic neuron activity.