Effects of cholinergic drugs on hypothalamic self-stimulation response rates of dogs

¹ Department of Pharmacology, School of Medicine and Dentistry, The University of Rochester, Rochester, New York

The administration of an anticholinesterase agent (physostigmine) which is capable of crossing the blood-brain barrier resulted in a marked and significant increase in threshold and depression of intracranial self-stimulation response rates in dogs with electrodes in the area of the medial mammillary nucleus of the hypothalamus. This effect was not manifested by an anticholinesterase agent (neostigmine) which does not penetrate the blood-brain barrier. The inhibitory action of physostigmine was blocked by the prior administration of an anticholinergic agent (atropine) capable of penetrating the blood-brain barrier, but not by an agent (methylatropine) incapable of penetrating the blood-brain barrier. The level of cholinesterase activity of the serum or red blood cells paralleled the degree of inhibition of self-stimulation response rates. Per cent inhibition of serum cholinesterase activity may be used as an index of per cent inhibition of "true" cholinesterase activity.

Key Words: cholinergic mechanism • physostigmine • neostigmine • atropine • Methylatropine • central nervous system behavior

Submitted on March 4, 1963

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