Muscarinic receptor alterations following neostigmine treatment

Male mice administered neostigmine in the drinking water a daily increasing concentrations (20-100 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 alpha- and beta-adrenoceptor 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.