Abstract
Male mice administered neostigmine in the drinking water at daily increasing concentrations (20–1000 mg/l) for four days became tolerant to its toxicity and presented a reduced binding of [ 3H]quinuclidinyl benzilate ([ 3H]QNB) in the small intestine. An increased binding of [ 3H]QNB was found in the forebrains of neostigmine-treated animals. This was due to an increase in muscarinic cholinergic receptor density. Neostigmine-treated animals were also more sensitive than control to the hypothermic effect induced by oxotremorine. Dopaminergic and α- and β-adrenoceptors were not affected. Administration of methylatropine together with neostigmine prevented the decrease of [ 3H]QNB binding in the small intestine as well as the increase in the forebrain.
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