Neurotransmitter release and its presynaptic modulation in the rat hippocampus after selective damage to cholinergic or/and serotonergic afferents.
Male Long-Evans rats sustained injections of 5,7-dihydroxytryptamine (5,7-DHT) into the fimbria-fornix and the cingular bundle or/and intraseptal injections of 192 IgG-saporin to induce serotonergic or/and cholinergic hippocampal denervations; Sham-operated rats served as controls. Four to ten weeks after lesioning, we measured (i). the electrically evoked release of acetylcholine ([3H]ACh), noradrenaline ([3H]NA) and serotonin ([3H]5-HT) in hippocampal slices in the presence of drugs acting on auto- or heteroreceptors, (ii). the nicotine-evoked release of NA and (iii). the choline acetyltransferase (ChAT) activity and the concentration of monoamines in homogenates. Saporin lesions reduced the accumulation of [3H]choline, the release of [3H]ACh and the ChAT activity, but increased the concentration of NA and facilitated the release of [3H]NA evoked by nicotine. 5,7-DHT lesions reduced the accumulation and the release of [3H]5-HT, the concentration of 5-HT, and also facilitated the release of [3H]NA evoked by nicotine. Accumulation and electrically evoked release of [3H]NA were not altered by either lesion. The combination of both toxins resulted in an addition of their particular effects. The 5-HT(1B) receptor agonist, CP 93129, and the muscarinic agonist, oxotremorine, reduced the release of [3H]ACh in control and 5,7-DHT-lesioned rats; in rats injected with saporin, their effects could not be measured reliably. CP 93129 and the alpha(2)-adrenoceptor agonist, UK 14304, reduced the release of [3H]5-HT in all groups by about 65%.


CONCLUSIONS
(i). selective neurotoxins can be combined to enable controlled and selective damage of hippocampal transmitter systems; (ii). 5-HT exerts an inhibitory influence on the nicotine-evoked release of NA, but partial serotonergic lesions do not influence the release of ACh at a presynaptic level and (iii). presynaptic modulatory mechanisms involving auto- and heteroreceptors may be conserved on fibres spared by the lesions.
Birthelmer
A
A
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Universität Freiburg, Neuropharmakologisches Labor, Hansastrasse, Germany.
Ehret
A
A
Amtage
F
F
Förster
S
S
Lehmann
O
O
Jeltsch
H
H
Cassel
J-C
JC
Jackisch
R
R
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000032:analysis / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D009699:N-Glycosyl Hydrolases; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D009924:Organ Culture Techniques; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
C085696:192 IgG-saporin; D000316:Adrenergic alpha-Agonists; D000911:Antibodies, Monoclonal; D015306:Biogenic Monoamines; D018678:Cholinergic Agents; D000922:Immunotoxins; D009498:Neurotoxins; D018722:Nicotinic Agonists; D011725:Pyridines; D011758:Pyrroles; D011810:Quinoxalines; D054789:Ribosome Inactivating Proteins, Type 1; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D000068438:Brimonidine Tartrate; D009538:Nicotine; D002795:Choline O-Acetyltransferase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine; D009638:Norepinephrine