Purinergic receptors in psychiatric disorders

Abstract

Psychiatric disorders describe different mental or behavioral patterns, causing suffering or poor coping of ordinary life with manifold presentations. Multifactorial processes can contribute to their development and progression. Purinergic neurotransmission and neuromodulation in the brain have attracted increasing therapeutic interest in the field of psychiatry. Purine nucleotides and nucleosides are well recognized as signaling molecules mediating cell to cell communication. The actions of ATP are mediated by ionotropic P2X and metabotropic P2Y receptor subfamilies, whilst the actions of adenosine are mediated by P1 (A1 or A2) adenosine receptors. Purinergic mechanisms and specific receptor subtypes have been shown to be linked to the regulation of many aspects of behavior and mood and to dysregulation in pathological processes of brain function. In this review the recent knowledge on the role of purinergic receptors in the two most frequent psychiatric diseases, major depression and schizophrenia, as well as on related animal models is summarized. At present the most promising data for therapeutic strategies derive from investigations of the adenosine system emphasizing a unique function of A2A receptors at neurons and astrocytes in these disorders. Among the P2 receptor family, in particular P2X7 and P2Y1 receptors were related to disturbances in major depression and schizophrenia, respectively. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'.

Keywords: ATP; Adenosine; Dopamine; GABA; Glutamate; Major depression; Mood; Purine receptors; Schizophrenia; Sensitization.