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Science 17 January 1969:
Vol. 163. no. 3864, pp. 299 - 301
DOI: 10.1126/science.163.3864.299
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Articles

Facilitation of Brain Self-Stimulation by Central Administration of Norepinephrine

C. David Wise 1 and Larry Stein 1

1 Wyeth Laboratories, Philadelphia, Pennsylvania 19101

Rats with electrodes implanted in the medial forebrain bundle stimulated their own brains at sharply reduced rates after systemic administration of disulfiram or intraventricular administration of diethyldithiocarbamate. Both drugs inhibit dopamine-beta-hydroxylase, the enzyme responsible for the final step in the biosynthesis of norepinephrine. The suppressed behavior was reinstated by intraventricular injections of 1-norepinephrine, but not by injection of its biologically inactive isomer, d-norepinephrine. Intraventricular administration of dopamine and serotonin did not restore self-stimulation. The rewarding effect of medial forebrain bundle stimulation may depend on the availability of norepinephrine as a transmitter, but not on dopamine or serotonin.


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