Nicotine effects in mouse hippocampus are blocked by mecamylamine, but not other nicotinic antagonists.
Previous data indicated that bath-application of nicotine to mouse hippocampal slices resulted in a concentration-dependent increase in the amplitude of the orthodromic population spike and the appearance of multiple population spikes in the CA1 pyramidal cell layer. d-Tubocurarine (4-100 microM), alpha-bungarotoxin (10-160 microM), and atropine (40-200 microM) had similar effects, although for alpha-bungarotoxin these excitatory effects were transient. Mecamylamine (1.6-3.2 mM) inhibited the population spike, while hexamethonium (3.2 mM) had no effect. These cholinergic antagonists were tested for their ability to block excitatory effects of nicotine (800 microM) at antagonist concentrations which were at or near threshold for intrinsic effects. Of the 5 antagonists tested, only mecamylamine (400 microM) effectively inhibited the nicotine-induced increase of the population spike amplitude and the appearance of multiple population spikes. These results suggest that nicotine exerts electrophysiological effects via a subclass of nicotinic cholinergic receptors that is neither neuromuscular nor ganglionic in the classical sense; these brain nicotinic receptors are sensitive to mecamylamine, but not to hexamethonium, alpha-bungarotoxin, or D-tubocurarine.
Freund
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RK
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
Jungschaffer
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DA
Collins
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AC
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008464:Mecamylamine / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic / Q000502:physiology*
D002038:Bungarotoxins; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D001285:Atropine