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

Abstract

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 noradrenergic cells. Pharmacological experiments have been made to ascertain which catechols contribute to this in vivo current. Monoamine oxidase inhibition by pargyline was followed by a total and rapid suppression of the in vivo signal. Blockade of dopamine-beta-hydroxylase by FLA-63 induced a significant increase in the electrochemical signal. Post-mortem analysis of LC catechol levels after administration 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-dihydroxyphenylacetic acid (DOPAC) were significantly increased. 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 alpha-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 of ibotenic acid (10 micrograms). 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-mortem 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 noradrenergic cell bodies.