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Science 12 March 1971:
Vol. 171. no. 3975, pp. 1032 - 1036
DOI: 10.1126/science.171.3975.1032
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Articles

Possible Etiology of Schizophrenia: Progressive Damage to the Noradrenergic Reward System by 6-Hydroxydopamine

Larry Stein 1 and C. David Wise 1

1 Wyeth Laboratories, Inc., Philadelphia, Pennsylvania 19101

Single or repeated intraventricular injections of 6-hydroxydopamine caused marked and long-lasting deficits in brain self-stimulation and other rewarded behaviors in the rat. The behavioral deficits, as well as the depletion of brain norepinephrine induced by 6-hydroxydopamine, were prevented by prior treatment with chlorpromazine. Episodic or continuous formation of endogenous 6-hydroxydopamine in man as a result of a genetically determined enzymatic error could selectively damage the binding capacity and, eventually, the structural integrity of the noradrenergic reward mechanism. Such damage might cause the fundamental symptoms and long-term downhill course of schizophrenia.


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