Catecholamine Metabolism in Locus Coeruleus Neurons: A Study of its Activation by Sciatic Nerve Stimulation in the Rat.

Abstract

Sciatic nerve stimulation, which strongly activates noradrenergic locus coeruleus (NA-LC) neurons, was used in anaesthetized rats as a model to study the transneuronal control of catechol metabolism in this nucleus. We show, using in vivo electrochemistry and biochemical post-mortem assays, that a prolonged (20 min) unilateral sciatic nerve electrical stimulation led to a reversible enhancement (80 - 130%) of both endogenous and in vivo extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) within the contralateral LC region. An elevation in DOPAC levels was also observed in the ipsilateral nucleus but was always significantly lower. The response was abolished by a pretreatment with kynurenic acid, a non-selective excitatory amino acid (EAA) antagonist known to block footshock-induced excitations of NA-LC neurons: in antagonist-treated rats, the stimulation induced a non-significant effect (+ 30%) on endogenous DOPAC levels, which contrasted with the highly significant effect (+ 113%) observed in vehicle-treated animals. As the major source of EAA afferents to the LC originates in the nucleus paragigantocellularis, we made an attempt to suppress activation by a section of these fibres. An incision performed obliquely (45 degrees ) between LC and PGi greatly and significantly attenuated, but did not totally suppress, the increase in DOPAC endogenous content due to the stimulation. These experiments indicate that a peripheral stimulus provokes an activation of catecholamine metabolism within the soma - dendritic region of the NA-LC cells. They suggest that this effect may be mediated, at least in part, by afferent pathways originating from the medulla which utilize an EAA as transmitter.