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Trends Pharmacol Sci. 2004 Aug;25(8):402-6.

How antipsychotics become anti-"psychotic"--from dopamine to salience to psychosis.

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  • 1Centre for Addiction and Mental Health, and the University of Toronto, 33 Russell Street Toronto, Ontario M5S 2S1, Canada.

Abstract

The relationship between dopamine, psychosis and antipsychotics has been challenged by the suggestion that there is a delay, of weeks, between the onset of dopamine receptor blockade and improvement in psychosis. However, recent data show that there is no significant delay. In light of these new findings, it is proposed that dopamine, through its role in reward prediction and motivational salience, provides a link to psychosis. Psychosis results from aberrant reward prediction and aberrant attribution of salience that is caused by disordered dopamine transmission. Antipsychotics become anti-"psychotic" by blocking dopamine transmission and attenuating the motivational salience of the symptoms, leading to the common statement from patients that symptoms "don't bother me as much anymore". This attenuation of salience also impacts on normal motivational drives, providing an explanation for why antipsychotics might induce iatrogenic negative symptoms and dysphoria, often leading to non-compliance by patients. The implications of this framework for relapse and other clinical phenomena, animal models and future studies are discussed.

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