Central and peripheral muscarinic actions of physostigmine and oxotremorine on avoidance responding of squirrel monkeys

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Abstract
The involvement of central and peripheral muscarinic cholinergic receptors in the behavioral effects of the cholinesterase inhibitor physostigmine was evaluated by comparing the ability of atropine and methylatropine to reverse the effects of physostigmine, the muscarinic agonist oxotremorine, or their quaternary analogs neostigmine and oxotremorine-M. Avoidance behavior was maintained under a schedule in which every lever press postponed delivery of electric shock for 20 s; shock occurred every 5 s in the absence of responding. Cumulative doses of physostigmine or oxotremorine produced dose-related decreases in response rates, and increases in response durations and rates of shock delivery. Similar effects occurred with neostigmine and oxotremorine-M. Methylatropine completely prevented the behavioral and parasympathetic effects of neostigmine and oxotremorine-M without having any behavioral effects of its own. However, methylatropine did not alter the behavioral effects of physostigmine or oxotremorine. Atropine prevented the peripheral manifestations as well as the behavioral effects of physostigmine and oxotremorine even though atropine decreased avoidance responding when given alone. These results suggest that in squirrel monkeys, central and peripheral muscarinic receptors may function in a redundant manner to control agonist-induced decrements in avoidance. When physostigmine or oxotremorine was given in conjunction with atropine, rates of avoidance responding were increased to 180% of control levels. Response rate increases after administration of oxotremorine or physostigmine in monkeys treated with atropine may reflect a non-muscarinic action of atropine, unmasked by the presence of cholinomimetics.