Regulatory effects of acutely repeated nicotine treatment towards central muscarinic receptors.
Sensitivity of brain muscarinic acetylcholine receptors to the agonists was examined in nicotine tolerant animals which were developed by acutely repeated injections of nicotine. In conscious rats, the dose-response curves of muscarinic agonists arecoline and pilocarpine, cholinesterase inhibitors soman and physostigmine rather than GABA receptor antagonist pentylenetetrazol or glycine receptor antagonist strychnine for producing EEG seizures were shifted leftwards by acutely repeated injections of nicotine. This phenomenon could be prevented by nicotinic antagonist mecamylamine. Similar results were obtained in acute nicotine tolerant mice and rabbits. In other experiments, the dose-response curve of arecoline-induced convulsions or oxotremorine-induced tremors was also shifted leftwards, and the durations of arecoline- and oxotremorine-induced tremors were prolonged in acute nicotine tolerant mice. In addition, the effects of arecoline for producing down-regulation of muscarinic receptors of rat cerebrum and hippocampus rather than brain stem were potentiated in acute nicotine tolerant rats. It is concluded that the sensitivity of brain muscarinic receptor to its agonists is increased in acute nicotine tolerant rats, mice and rabbits.
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
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D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation; D004569:Electroencephalography; D005260:Female; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000378:metabolism
D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D009538:Nicotine