Effects of physostigmine on rat brain acetylcholine, acetylcholinesterase and conditioned pole jumping

Abstract

The present study was designed to provide evidence that the behavioral effects of physostigmine are related to inhibition of brain acetylcholinesterase (AChE). Adult male Holtzman rats were trained to pole jump to a buzzer as the conditioned stimulus and to electric shock to the grid floor as the unconditioned stimulus. All drugs were given S.C. as base. Physostigmine (0.125-0.25 mg/kg) depressed pole jump behavior in methyl a&opine (2.1 mg/kg) or saline-treated rats. (-) Hyoscyamine (1 mg/kg) blocked the actions of physostigmine, suggesting a central site of action. Total brain acetylcholine (ACh) and AChE were determined in various groups of animals. The increase in brain ACh and the decrease in AChE activity were negatively correlated in physostigmine-treated rats. These changes were highly correlated during the onset and peak of physostigmine behavioral effects but not during the recovery period. Although (-) hyoscyamine antagonized the behavioral effects of physostigmine, it did not alter the increase in brain ACh or decrease in brain AChE. It is concluded that most of the behavioral effects of physostigmine are related to central AChE inhibition.

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

“…Rather, muscarinic receptors in the CNS and PNS may function redundantly under these conditions to influence avoidance responding of squirrel monkeys. Reports that methylatropine produced partial prevention of the behavioral effects of physostigmine (Vaillant 1964;Rosecrans et al 1968;Rosecrans and Domino 1974) further emphasize the contribution of peripheral muscarinic actions to the behavioral effects of physostigmine.…”

“…From these data alone, however, it is not possible to distinguish a pure CNS action from a dual peripheral and central mechanism of action wherein both CNS and PNS actions function redundantly to control behavior. Moreover, the peripherally-acting antagonist, methylatropine, has been reported by some investigators to function as a partial antagonist of behavioral effects of physostigmine (Vaillant 1964;Rosecrans et al 1968;Rosecrans and Domino 1974).…”

“…Behavioral effects of physostigmine based upon this action could thus involve muscarinic and/or nicotinic cholinergic receptors. Analysis of the mechanisms of action of physostigmine is further complicated by the non-cholinergic actions of this class of drugs that may be relevant to their behavioral pharmacology (Aprison 1962;Goldberg et al 1965;Carbera et al 1966) Muscarinic antagonists do not always completely block behavioral effects of physostigmine (Vaillant 1967;Rosecrans et al 1968;Rosecrans and Domino 1974;Chait and Balster 1979).…”

Effects of physostigmine on brain acetylcholine content and release

“…Under such experimental conditions it is impossible, considering physostigmine-induced cholinesterase inhibition, to reveal a decreasing effect of physostigmine on brain ACh content. The finding that physostigmine reduces slightly the elevated cortical levels of ACh in pentobarbital anaesthetized animals is, of course, in complete agrement with the data of others that physostigmine alone elevated brain ACh above control levels (BEANI et al, 1969;CROSSLAND and SLATER, 1968;FISCHER et al, 1969;MALPICA et al, 1970;MECAZZINI et al, 1965;ROSECRANS et al, 1968). The ability of physostigmine to reduce cortical ACh content pfobably is due to its ACh releasing property.…”

“…It is well known that physostigmine increases total brain acetylcholine (ACh) content (PAZZAGLI and PEPEU, 1964;ROSECRANS, DREN and DOMINO, 1968;MALPICA, JURUPE and CAMPOS, 1970). However, the per cent increase in regional brain ACh varies markedly (FISCHER, WESTERMANN and OELSSNER, 1969;MEGAZZINI, BERNARDI and BALLOT'& 1965).…”