An effect of physostigmine on the central nervous system of rabbits, related to brain levels of norepinephrine

Abstract

The effect of physostigmine on EEG activity and on thalamocortical recruitment was evaluated in otherwise untreated rabbits in which brain levels of norepinephrine were lowered by either reserpine or α-methyl- p-tyrosme, and in animals in which tissue levels of norepinephrine were restored by the administration of pargyline and l-DOPA after initial depletion. Levels of norepinephrine in several brain parts were measured in the control animals and after the several pharmacological combinations. In control animals, physostigmine elicited a reversible desynchronization of the EEG and a reversible attenuation of the thalamocortical recruited potentials. Lowering of norepinephrine levels in the brain tissue by means of either reserpine or α-methyl- p-tyrosine did not alter the recruitment response but prevented block or attenuation of that response induced by the anticholinesterase. Restoration of catecholamine levels in brain tissue by the administration of pargyline followed by l-DOPA to the animals treated with reserpine or α-methyl- p-tyrosine reestablished the physostigmine blockade of recruitment. These results are discussed in terms of the central involvement between cholinergic and catecholaminergic systems; certain speculations as to the significance of antirecruitment and desynchronizing action of anticholinesterases (and acetylcholine) are also presented.