Brain Research, 273 (1983) 197-206 197 Elsevier Research Reports Catecholamine Metabolism in the Rat Locus Coeruleus as Studied by In Vivo Differential Pulse Voltammetry. I. Nature and Origin of Contributors to the Oxidation Current at + 0.1 V MICHEL BUDA, GRAZIA DE SIMONI*, FRANCOIS GONON and JEAN-FRANCOIS PUJOL Dbpartement de Mbdecine Expbrimentale, I N S E R M U171, 8, A venue Rockefeller, 69008 Lyon (France) (Accepted December 28th, 1982) Key words: locus coeruleus - catecholamine metabolism - in vivo voltammetry - noradrenaline - 3,4-dihydroxyphenylacetic acid Differential pulse voltammetry was used together with treated carbon fiber microelectrodes to study the in vivo catecholamine (CA) metabolism in the locus coeruleus (LC), a brain region densely packed with noradrenergic neurons. In chronically implanted rats, an in vivo oxidation current that peaks at + 0.1 V has been detected inside the LC complex. This current whose potential is characteristic of the oxidation of the catechols, had the same anatomical localization as the noradren- ergic cells. Pharmacological experiments have been made to ascertain which catechols contribute to this in vivo current. Monoamine oxi- dase inhibition by pargyline was followed by a total and rapid suppression of the in vivo signal. Blockade of dopamine-fl-hydroxy- lase by FLA-63 induced a significant increase in the electrochemical signal. Post-mortem analysis of LC catechol levels after ad- ministration of this drug revealed a considerable decrease in NA and its major catechol metabolite, 3,4-dihydroxyphenylglycol (DOPEG) although DA and its metabolite 3,4-dihydroxyphenylaceticacid (DOPAC) were significantlyincreased. Comparison of these results led us to conclude that DOPAC is probably the most important contributor to the in vivo oxidation current. This assertion is corroborated by results obtained after tyrosine hydroxylase inhibition with a-methyl-p-tyrosine: the in vivo catechol current was rapidly suppressed and post-mortem levels of DOPAC were significantly reduced while DOPEG remained almost normal. An attempt was made to selectively destroy the LC cell bodies by a unilateral injection ofibotenic acid (10/tg). Eight to 15 days after injection, no current was detectable in the injected side although it was still present in the contralateral intact side. Post-mor- tem levels of DOPAC and DOPEG levels of the lesioned side were 29% and 17%,respectively, of those in the intact side. Thus, we assumed that the in vivo catechol current in the LC comes from the oxidation of DOPAC most probably synthesized by the nor- adrenergic cell bodies. INTRODUCTION In vivo electrochemical detection of catechols has been the subject of numerous investiga- tions 3"4'8'9"t3't4"2°. Most of these studies have been focused on highly innervated dopaminergic re- gions such as the striatum. Several investigators have interpreted the in vivo variations of the electrochemical current as corresponding to variations in dopamine (DA) release ~3.~4,20. These conclusions appear to be highly controversial in the light of recent studies4.8,9.Indeed, the electro- chemical measurements of catechols is compli- cated by the presence of high levels of brain as- corbic acid (AA). Thus, with electrodes which cannot distinguish DA and AA, the interpreta- tion of the in vivo amperometric results is ex- tremely complex5, especially considering that AA levels are alsosubject to variations 4.9. Re- cently we used differential pulse voltammetry in conjunction with treated pyrolytic carbon fiber microelectrodes to monitor catechols in differ- * Present address: Istituto Mario Negri, via Eritrea 62, Milano, Italy. 0006-8993/83/$03.00 © 1983 Elsevier Science Publishers B.V.