Sympathetic sprouting: no evidence for muscarinic modulation of noradrenaline release in hippocampal slices of rats with fimbria-fornix lesions

Lesions of the septohippocampal pathways elicit sprouting of sympathetic fi bers from the superior cervical ganglion, a phenomenon which, within a few months, raises the hippocampal noradrenaline (NA) content above normal. In peripheral sympathetic fibers, the release of NA is modulated via presynapt ic muscarinic receptors. Such receptors have not been detected so far on te rminals of noradrenergic neurons originating in the locus coeruleus. Whethe r the release of NA could become sensitive to muscarinic modulation in the hippocampus following sympathetic fiber ingrowth was the major question in this experiment. The contribution of presynaptic nicotinic receptors was al so studied. Slices from the ventral hippocampus (only dentate gyrus+CA3 reg ion) of sham-operated (SHAM) and fimbria-fornix lesioned (LES) Long-Evans r ats (8-10 months after surgery) were preincubated with [H-3]NA and stimulat ed either once (S-1) with 100 mu M nicotine or (in parallel experiments); t wice electrically (S-1, S-2), using conditions (six pulses 100 Hz, 2 ms, 28 mA, 4 V/chamber) that precluded autoinhibition. In experiments using elect rical stimulation, the superfusion medium contained desipramine (1 mu M). I n LES rats, the tissue NA content had almost doubled (171% of SHAM levels), but the amount of [H-3]NA taken up by the slices was unchanged, and the ov erflow evoked at S-1 by both nicotinic and electrical stimulation was signi ficantly reduced in comparison with SHAM rats. In both groups, the addition of oxotremorine or oxotremorine+atropine (1 mu M, each) before S-2 failed to affect the electrically evoked overflow of H-3. Nicotine-induced NA rele ase was inhibited by hexamethonium (100 mu M) in both groups, although sign ificantly less potently in LES rats. Tissue activity of choline acetyltrans ferase was reduced in LES rats to 15% of SHAM levels and the 5-hydroxytrypt amine content was also strongly diminished (38% of SHAM values). It is conc luded that lesion-induced sprouting of sympathetic fibers into the hippocam pus is not accompanied by the emergence of a muscarinic modulation of NA re lease in this tissue, and that the sensitivity of the presynaptic stimulato ry effect of nicotine was modified by the lesion.