The objective of this study was to examine the effect of neuronal impulse flow on the acetylcholine-dcpleting action of hemicholinium-3 (HC-3). We utilized electrolytic interruption of cholinergic axons and administration of pentobarbital as means to stop or slow impulse flow or release in cholinergic scptal-hippocampal neurones. It has been reported previously that placement of lesions in the septum results in a large rise in acetylcholine (ACh) levels in the hippocampus at short times post-lesion (0.5 3 hr). Administration of pentobarbital has a similar effect. When HC-3 was injected immediately prior to the placement of septal lesion, the post-lesion increase in ACh levels in the hippocampus were blocked. However, if HC-3 was administered 30 min after the placement of lesion, a time at which the post-lesion increases have already occurred, then HC-3 appeared to have no effect. In the striatum, a region which does not receive the cholinergic input from the septum and which should not be effected by placement of septal lesions, there was a depletion of acetylcholine caused by the administration of HC-3. The finding that HC-3 administration blocks the post-lesion rise in ACh levels, suggests that this post-lesion rise requires new synthesis of ACh and hence a supply of extracellular choline which is blocked by HC-3. Our finding that the HC-3 depleting effect was blocked 30 min after lesion, is consistent with the notion that the action of HC-3 is dependent on neuronal impulse flow. However it can be more broadly stated that HC-3 will have a reduced depleting action after any treatment resulting in a depression of acetylcholine synthesis rate.
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience