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

Abstract

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.