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

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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°) 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.

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