Physostigmine-insensitive behavioral excitatory effects of atropine in squirrel monkeys

Lever press responses of squirrel monkeys were maintained under a multiple schedule in which the first response after 3 min produced either food or electric shock depending on the prevailing stimulus. Atropine sulfate (0.3-3 mg/kg, IM) given immediately before experimental sessions disrupted the temporal pattern of responding and produced dose-related decrease in rates of food- and shock-maintained responding. Increases in responding occurred when 1 mg/kg atropine was given 1 to 12 hr prior to experimental sessions. A maximal increase of 200% of control rates was seen following the 2-hr pretreatment. Qualitatively similar effects were obtained with scopolamine suggesting that the time-dependent increases may be a general consequence of muscarinic receptor blockade. Response patterning changes and response rate increases were also produced by coadministration of atropine and physostigmine both given immediately before the session. Increases in rates of responding have also been observed previously after administration of atropine with rate-decreasing doses of the direct-acting muscarinic agonist oxotremorine. Physostigmine did not reverse the rate increases or the alteration in temporal patterning produced by the 2-hr atropine pretreatment; rate decreases induced by immediate pretreatment with atropine were blocked by physostigmine. Thus, the response rate-decreasing effects of atropine were distinct from its rate-increasing effects. Whereas the rate-decreasing effects of atropine appear to involve muscarinic receptors, increases in responding may not. Such nonmuscarinic behavioral excitatory actions of atropine may be expressed when the muscarinic-related decreases are blocked by physostigmine or oxotremorine, or when the decreases are overridden by excessive nonmuscarinic stimulation, perhaps triggered by time-dependent changes in acetylcholine turnover associated with atropine.