doi: 10.1111/j.1472-8206.2004.00287.x REVIEW ARTICLE Dopamine, depression and antidepressants Eric Dailly*, Franck Chenu, Caroline E. Renard, Michel Bourin EA 3256 Neurobiologie de l’anxie ´te ´ et de la de ´pression, Faculte ´ de Me ´decine, BP 53508, 1 rue Gaston Veil, 44035 Nantes Cedex 01, France INTRODUCTION The monoamine hypothesis based on the deficiency of one or other monoamines is commonly evoked to explain the physiopathology of depression. This hypothesis, initially based on noradrenaline and serotonin defici- ency, is extended to dopamine. The implication of dopamine was suggested earlier by clinical observations. Thus, depression is a common disturbance in schizo- phrenia and Parkinson’s disease which are pathologies known to present with a dopamine central system dysfunction [1,2]. Moreover, there are similarities between symptoms of Parkinson’s disease, schizophrenia and depression. Some symptoms of depression such as anhedonia (inability to experience pleasure) and decreased motor activity are also observed in schizo- phrenia [3,4]. The symptoms of Parkinson’s disease such as psychomotor retardation and diminished motivation are common in depressed patients [5]. Biochemical evidence in patients with depression is derived from the study of homovanillic acid, a dopamine metabolite. Reduced venoarterial plasma concentration gradients of homovanillic acid were found in depressed patients [6]. This likely implication of dopamine in depressive illness was also proved by the technique of acute tyrosine depletion [7]. Tyrosine is the precursor of dopamine synthesis and results of neuropsychological tests of healthy volunteers with a reduction in tyrosine availab- ility to the brain paralleled those reported in previous investigations of unipolar depression. All these results are consistent with the hypothesis of a role of dopamine in depression physiopathology. To understand this role, data concerning dopamine cerebral pathways and receptors are shortly reviewed. From these elements, the relationships between dopamine, depression and antidepressants are examined. DOPAMINE PATHWAYS AND RECEPTORS IN THE CENTRAL NERVOUS SYSTEM Four main dopaminergic pathways were identified with- in the central nervous system. The ventral tegmental area is the place of origin of two projection pathways towards the cortex (the mesocortical pathway) and the limbic area (the mesolimbic pathway); the hypothalamus is the place of origin of a projection towards the pituitary gland which controls prolactin secretion (the tubero- infundibular pathway) and a dopaminergic projection extends from the substantia nigra to the striatum (the nigrostriatal pathway) the degeneration of which is implicated in Parkinson’s disease. Using these pathways, dopamine receptors are located. Five genes encoding dopamine receptors were identified. Keywords antidepressants, depression, dopamine Received 3 May 2004; revised 11 June 2004; accepted 5 July 2004 *Correspondence and reprints: eric.dailly@chu-nantes.fr ABSTRACT The relationship between depression and dopamine deficiency in the mesolimbic pathway has been hypothesized for many years. The experimental studies with animal models of depression and the human studies implicate the role of the dopamine system in depression. Not only do dopaminergic receptor agonists, but also antagonists such as olanzapine exhibit antidepressant effects associated with standard antidepressants in patients with treatment-resistant depression. This paradoxical result suggests that further investigations are necessary to understand the role played by dopamine in depression. Ó 2004 Blackwell Publishing Fundamental & Clinical Pharmacology 18 (2004) 601–607 601