Effects of physostigmine on brain acetylcholine content and release

Abstract

The content and release of acetylcholine (ACh) from cat brain and ACh content of rat brain was measured using the frog rectus and leech muscle bioassays before and after physostigmine 100 rg/kg i.v. or i.p. The drug elevates steady state levels of brain ACh of awake animals especially in the neocortex, caudate nucleus and hippocampus but much less so in the lateral geniculate and superior colliculus. Physostigmine was shown to produce neocortical release of ACh through a subcortical mechanism in brainstem transected cats and to decrease ACh neocortical content in pentobarbital anesthetized cats and rats. The neocortical release of ACh seems to be mediated primarily through a subcortical brain mechanism which is activated by physostigmine. It is postulated that the ascending reticular formation is involved. Local application of scopolamine (I pg/ml) into the collecting cup did not antagonize the effects of 100 pg/kg of physostigmine iv. as much as 1 mg/kg of scopolamine i.v. On the other hand, 2 mg/kg of mecamylamine given i.v. not only did not antagonize physostigmine-induced neocortical release of ACh, but seemed to enhance it. The results indicate a complex action of physostigmine on the cholinergic system of the brain.

The Pharmacology of Physostigmine

“…In cats, physostigmine (100 µgkg, i.v. or s.c.) elevated brain acetylcholine content, particularly in the neocortex, caudate nucleus and hippocampus, by 10% to 30% and in rat whole brain and cerebral cortex by 25 to 40% (22). Regionally selective increases in brain acetylcholine were also reported in the rat brain by Hallak and Giacobini (106) and in the guinea pig brain, where the largest increases occurred in the olfactory lobes, the parietal cortex, and the caudate nucleus.…”

The Effects of Paraoxon on Blood Pressure in the Anaesthetized and in the Conscious Rat

“…Nakagawa, 1968). Moreover, the effects by physostigmine cannot be attributed to inhibition of cholinesterase only (Cox & Lomas, 1972;Bartolini, Bartolini & Domino, 1973). and conscious rats in order to study its action.…”

Effects of Cholinomimetic Agents Given Into the Brain of Fowls

“…This could have been due to mixed muscarinic and nicotinic actions of acetylcholine or, since it was necessary to combine physostigmine with acetylcholine, to an action also of physostigmine on neurones. Certainly, physostigmine applied iontophoretically excites cat brain-stem neurones which are unaffected by acetylcholine (Salmoiraghi & Steiner, 1963;Bradley, Dhawan & Wolstencroft, 1966) (Bartolini, Bartolini & Domino, 1973).…”

“…Interactions of physostigmine with the cholinoceptive antagonists could also have complicated the interpretation. For example, cortical release of acetylcholine induced in cats by intravenous physostigmine was reduced by prior dosage with scopolamine but enhanced by mecamylamine (Bartolini, Bartolini & Domino, 1973).…”