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 ventral horn of the lumbar spinal cord in awake unrestrained rats using in vivo microdialysis coupled to a highly sensitive radioenzymatic assay. In normal animals, baseline NA output averaged 13.4 +/- 2.2 fmol/30 microliters. KCl (100 mM) or desipramine (5 microM) added to the perfusion fluid increased NA levels 11.2-fold and 2.2-fold, respectively, whereas neuronal impulse blockade by tetrodotoxin (1 microM) added in the presence of desipramine stimulation produced a 88% reduction of extracellular NA levels. Noradrenergic denervation of the spinal cord by either electrolytic destruction of the noradrenaline-containing axon terminals or intraventricular 6-hydroxydopamine produced, 3-4 weeks later, dramatic 84 and 91% reductions in baseline NA release associated to a marked loss of immunoreactive noradrenergic fibers throughout the spinal cord or caudal to the site of electrolytic damage and almost completely abolished responses to pharmacological manipulations. The results support the view that spinal extracellular NA levels are neuronally derived, also suggesting that noradrenergic neurotransmission in the ventral spinal cord largely (by at least 85%) depends on the integrity of descending brainstem afferents. The microdialysis technique, thus, appears to be a useful tool for future studies on strategies aimed at promoting reinnervation and functional recovery in the deafferented spinal cord.
Leanza
G
G
Institute of Human Physiology, University of Catania, Italy.
Maccavino
M C
MC
Stanzani
S
S
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000870:Anterior Horn Cells / Q000473:pathology / Q000502:physiology*; D003714:Denervation; D003891:Desipramine / Q000494:pharmacology; D005260:Female; D008161:Lumbosacral Region; D017551:Microdialysis; D009638:Norepinephrine / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D013779:Tetrodotoxin; D011189:Potassium Chloride; D003891:Desipramine; D009638:Norepinephrine