92 Abstracts of Papers

galantamin and eserine; but following the admin- istration of phenamine (amphetamine) low ampli- tude fast activity was induced after sectioning along the line connecting the superior c. quadrigemina and c. mamillaria and more rostrol sectioning the administration of eserinc, galantamin and phen- amine did not induce the EEG activation. Thus, we observe the EEG activation after galantamin and eserine injection when the cerebral cortex is connected with the midbrain. These experiments in sectioning the brain stem at diffprent levels suggest that the activating effect of anticholinestw- ase drugs depends on their influence upon the mid- brain reticular system and this fact shows the avail- ability of cholinergic structures in it and their role in the function of the reticular formation. The blocking effect of amisil upon the EEG activation produced by anticholinesterasr drugs, and the absence of such an effect with metacinc and chlor- promazine show an interaction between the central cholinolytic and cholinoreactive systems of the reticular formation.

312 A Pharmacological Demonstration of Cholin- ergic Mechanisms in the Central Nervous system. L. S. HARRIS (U.S.A.,I.

Previous studies, utilizing the photocell activity cage, have shown that various anti-cholinergic agents, scopolamine, atropine, trihexyphenidyl, etc. produce an increase in the spontaneous activity of mice.“’ The quaternary salts, which do not readily cross the blood-brain barrier, do not share this activity.

Tremorinc, which probably acts by cholinergic mechanisms , produces a decrease in spontaneous activity at non-tremorigenic doses. In addition to antagonizing the tremors produced by Tremorine, the centrally acting anti-cholinergics specifically reverse the depression of spontaneous activity prod- uced by this drug. The quaternary salts arc unable to produce this reversal.

Other non-quaternary cholinergic agents such as pilocarpine, and 2-dimethylaminoethylacetate (the tertiary amine ofacetylcholine), also cause a depres- sion of spontaneous activity and, at some doses, trrmors in mice. The tremors and depression of activity produced by these compounds can be reversed by the centrally active anti-cholinergics. In addition, small doses of the cholincsterase inhibi- tor eserine produce a depression of activity. This effect is obtainable in the presence of amounts of atropine methyl nitrate which completely protrct against the peripheral actions of eserine. Again, the depressant effects of 2.dimethylaminoethyl- acetate are markedly potentiated by eserine.

Thus, cholinergic agents and the anti-cholin- &erase eserine, which have access to the central nervous system, depress the spontaneous activity of mice. The anti-cholinergic agents stimulate the activity and readily reverse the depression produced by the cholinergic agents and Tremorine. These

findings will be discussed in relarion to cholinrrgic mediation in the central nervous system.

1. HARRIS, L. S. (1961), Fe‘erl. Proc., 20, 393.

3 I3 Amphetamine Induced Recovery of Condi- tioned Reflexes disturbed by Cholinolytics and Chlorpromazine. 11. 1v. LINUCII~V, N.J. LUCOMSKAJA, hl. J. ~~ICH~LSON and E. 1,. SHCHELKUNOV (U.S.S.R.).

Different cholinolytics induce disturbance\ in tht nervous activity of men and animals which can bc reduced or completely prevented by simultaneous injection of anticholinesterases: cserine, parooron, armine, prostigmine (hZichelson et al., 1954: 1957, 1959). Such antagonism could probably occur at the level of cholinergic structures participating in thr performance of nervous activity.

In healthy men the temporary disturbanct in mental activity inducrd by parpanite could bc reduced by the preliminary taking of amphetamine in thcraprutic dose.

The disturbance in motor-food conditioned reflrxes of rats in a labyrinth was induced by atropinr, parpanite and other cholinolytics. Thr preliminary or simultaneous injection of an ade- quate dose of amphetamine (0.5-2.0 mg/kgI com- pletrly or partly prevented the disturbance caused by cholinolytics.

The disturbance in the motor-food conditioned reflexes of rabbits and cats caused by benactyzinr could be reduced by injection of adequate doses of amphetamine.

Amphetamine restored to normal the motor-food and avoidance conditioned reflexes of rats disturbed by chlorpromazine. This antagonism occurred even in cases when a large range of doses of amphr- tamine and chlorpromazine, respectively, had been used.

The ability of ayphetamine to reduce the disturb- ances which cholinolytics caused in nervous activity probably could be explained as a manifestation of adaptative adrenergic influrnce on cholinergic brain synapses. Special features of the antagonism of chlorpromazine and amphetamine suppose another level, e.g. the adrenergic structures of thr brain stem reticular formation.

314 Relationship between Central Anticholinergic Actions and Antiparldnson Efficacy of Phenothiazine Derivatives. R. P. WHITE and E. J. bt’ESTERBE.KE (U.S.A.).

Ethopropazine (Parsidol) is employed clinically as an antiparkinson agent, whereas promethazine, thioridazine, promazine, prochlorperazine are not and, with the exception of several, have been reported to produce extrapyramidal overactivity toxic effects. Since Parkinsonism may result from an over-active cholinergic mechanism,“’ it sermed