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Journal of Neuroscience, Vol 5, 1307-1315, Copyright © 1985 by Society for Neuroscience
Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin
PB Clarke, RD Schwartz, SM Paul, CB Pert and A Pert
Three radioligands have been commonly used to label putative nicotinic
cholinoceptors in the mammalian central nervous system: the agonists
[3H]nicotine and [3H]acetylcholine ([3H]ACh--in the presence of atropine to
block muscarinic receptors), and the snake venom extract,
[125I]-alpha-bungarotoxin([125I]BTX), which acts as a nicotinic antagonist
at the neuromuscular junction. Binding studies employing brain homogenates
indicate that the regional distributions of both [3H]nicotine and [3H]ACh
differ from that of [125I]BTX. The possible relationship between brain
sites bound by [3H]nicotine and [3H]ACh has not been examined directly. We
have used the technique of autoradiography to produce detailed maps of
[3H]nicotine, [3H]ACh, and [125I]BTX labeling; near-adjacent tissue
sections were compared at many levels of the rat brain. The maps of high
affinity agonist labeling are strikingly concordant, with highest densities
in the interpeduncular nucleus, most thalamic nuclei, superior colliculus,
medial habenula, presubiculum, cerebral cortex (layers I and III/IV), and
the substantia nigra pars compacta/ventral tegmental area. The pattern of
[125I]BTX binding is strikingly different, the only notable overlap with
agonist binding being the cerebral cortex (layer I) and superior
colliculus. [125I]BTX binding is also dense in the inferior colliculus,
cerebral cortex (layer VI), hypothalamus, and hippocampus, but is virtually
absent in thalamus. Various lines of evidence suggest that the high
affinity agonist-binding sites in brain correspond to nicotinic cholinergic
receptors similar to those found at autonomic ganglia; BTX- binding sites
may also serve as receptors for nicotine and are possibly related to
neuromuscular nicotinic cholinoceptors.
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