NORADRENERGIC NEUROTRANSMISSION IN THE VENTRAL SPINAL-CORD - BASIC CHARACTERISTICS AND EFFECTS OF DENERVATING LESIONS, AS STUDIED IN THE AWAKE RAT BY MICRODIALYSIS

Extracellular levels of noradrenaline (NA) were measured in the ventra l horn of the lumbar spinal cord in awake unrestrained rats using in v ivo microdialysis coupled to a highly sensitive radioenzymatic assay. In normal animals, baseline NA output averaged 13.4 +/- 2.2 fmol/30 mu l KCl (100 mM) or desipramine (5 mu M) added to the perfusion fluid i ncreased NA levels 11.2-fold and 2.2-fold, respectively, whereas neuro nal impulse blockade by tetrodotoxin (1 mu M) added in the presence of desipramine stimulation produced a 88% reduction of extracellular NA levels. Noradrenergic denervation of the spinal cord by either electro lytic destruction of the noradrenaline-containing axon terminals or in traventricular 6-hydroxydopamine produced, 3-4 weeks later, dramatic 8 4 and 91% reductions in baseline NA release associated to a marked los s of immunoreactive noradrenergic fibers throughout the spinal cord or caudal to the site of electrolytic damage and almost completely aboli shed responses to pharmacological manipulations. The results support t he view that spinal extracellular NA levels are neuronally derived, al so suggesting that noradrenergic neurotransmission in the ventral spin al cord largely (by at least 85%) depends on the integrity of descendi ng brainstem afferents. The microdialysis technique, thus, appears to be a useful tool for future studies on strategies aimed at promoting r einnervation and functional recovery in the deafferented spinal cord.