Effects of physostigmine on brain acetylcholine content and release.

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.