Cholinergic control of catechol metabolism in the rat locus coeruleus as studied by in vivo voltammetry

Differential pulse voltammetry with treated carbon fibre electrodes was used to study the effect of cholinergic drugs on the metabolism of locus coeruleus (LC) noradrenergic cells in vivo. A catechol peak corresponding to DOPAC synthesized by noradrenergic cells and reflecting their metabolic activity, was recorded every two minutes in the LC of freely moving rats. Cholinergic agonists like eserine (0.5 mg/kg s.c.) and oxotremorine (0.1 and 0.4 mg/kg s.c.) increased the DOPAC peak. This effect seemed to be mediated by muscarinic receptors since it was antagonized by scopolamine (5 mg/kg i.p.). Oxotremorine in high doses (1.5 mg/kg s.c. for 3 days) induced 'delayed activation' of tyrosine hydroxylase (+273%). In these conditions LC cells were no longer responsive to a challenge dose of oxotremorine though they maintained normal responsiveness to noradrenergic drugs. The results show that cholinergic drugs can greatly influence the metabolism of LC noradrenergic neurons.