Release of [3H]acetylcholine from rat hippocampal slices: effect of septal lesion and of graded concentrations of muscarnic agonists and antagonists.

To establish the existence and sensitivity of presynaptic muscarinic receptors on central cholinergic neurons, the electrically evoked release of [3H]ACh from hippocampal slices was measured after medial septal lesion or in the presence of graded concentrations of muscarinic agonists and antagonists. One week after septal lesion, the evoked release of [3H]ACh was abolished, indicating that septo-hippocampal cholinergic fibres are the source of this release. The muscarinic agonists, Oxotremorine, carbamylcholine and arecoline reduced the rate of evoked release of [3H]ACh with an ED50 similar to the ED50 required to displace specific [3H]quinuclidinyl benzilate (QNB) binding as found by Yamamura and Snyder. However, the antagonists QNB, antropine and scopolamine were 10 times weaker in increasing the rate of [3H]ACh release than in displacing [3H]QNB binding. Results suggest that the lower affinity of muscarinic antagonists to presynaptic receptors prevents the demonstration of the specific labelling of these receptors with [3H]QNB.