Pharmacodynamic effects of nicotine and acetylcholine biosynthesis in mouse brain.
Nicotine (4; 8 mg/kg) given intraperitoneally to mice had a marked hypothermic effect with a duration of more than 2 hours. Mecamylamine (0.5; 2.5 mg/kg) prevented the hypothermic effect of 2 mg/kg nicotine but had no effect on 4 mg/kg nicotine. Atropine (5 mg/kg) did not affect the hypothermia produced by nicotine. Other symptoms induced by nicotine (0.5-4 mg/kg) were convulsions, rigidity, tremor and decrease in motor activity. Pretreatment with mecamylamine (0.5 mg/kg) prevented convulsions but had only a slight effect on the decreased motor activity. Atropine pretreatment was ineffective. It thus seems as if the effects of nicotine at least to some part are mediated by nicotine-like receptors. When a tracer dose of labelled choline (3H-Ch) was given to mice treated with nicotine (4 mg/kg) a marked increase (+100%) in the biosynthesis of labelled acetylcholine (ACh) in the striatum was found when the animals were killed by decapitation. If the mice were killed by a more rapid technique, microwave irradiation of the head, no change in 3H-ACh formation was observed in comparison to controls. The findings indicate that nicotine can preserve a very labile pool of newly synthesized ACh in the striatum.
D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001711:Biotransformation; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D005260:Female; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism
D008464:Mecamylamine; D009538:Nicotine; D001285:Atropine; D002794:Choline; D000109:Acetylcholine