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.
Tests in which an animal receives or avoids direct electrical stimulation of its brain according to its position in the tank as well as tests of free operant behavior demonstrate the existence of both positively and negatively rewarding areas in the brain of the goldfish.
Intracranial self-stimulation experiments in the dog using a two-wire electrode, with each wire used as a monopolar electrode and the combination as a bipolar electrode, show that monopolar stimulation may produce either a higher or a lower rate of response than that produced by bipolar stimulation. A theoretical consideration of the changes in current density around the electrode when it is changed from a monopolar to a bipolar electrode shows that such differences are to be expected. The exact location of the structure being stimulated with reference to the two electrode tips will determine whether the structure is subjected to a higher current density on monopolar or on bipolar stimulation.
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