Antidepressant- and anticompulsive-like effects of purinergic receptor blockade: Involvement of nitric oxide

Author(s)

Pereira, Vitor S. ^[1] ; Casarotto, Plinio C. ^[1] ; Hiroaki-Sato, Vinicius A. ^[1] ; Sartim, Ariandra G. ^[2] ; Guimaraes, Francisco S. ^{[3, 1]} ; Joca, Samia R. L. ^{[3, 2]}

Affiliation

^[1] Campus USP, Sch Med, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Campus USP, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14040904 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo - Brazil

• Document type: Journal article
• Source: European Neuropsychopharmacology; v. 23, n. 12, p. 1769-1778, DEC 2013.
• Web of Science Citations: 25

Abstract

Activation of purinergic receptors by ATP (P2R) modulates glutamate release and the activation of post-synaptic P2R is speculated to induce nitric oxide (NO) synthesis. Increased glutamatergic and nitrergic signaling have been involved in the neurobiology of stress-related psychiatric disorders such as anxiety and depression. Therefore, the aim of this study was to test the effects of two P2R antagonists (PPADS and iso-PPADS) in animals submitted to models predictive of antidepressant-, anxiolytic- and anticompulsive-like effects. Swiss mice receiving PPADS at 12.5 mg/kg showed reduced immobility time in the forced swimming test (FST) similarly to the prototype antidepressant imipramine (30 mg/kg). This dose was also able to decrease the number of buried marbles in the marble-burying test (MBT), an anticompulsive-like effect. However, no effect was observed in animals submitted to the elevated plus maze (EPM) and to the open field test. The systemic administration of iso-PPADS, a preferential P2XR antagonist, also reduced the immobility time in FST, which was associated to a decrease in NOx levels in the prefrontal cortex. In addition, P2X7 receptor was found co-immunoprecipitated with neuronal nitric oxide synthase (NOS1) in the prefrontal cortex. These results suggest that P2X7, possibly coupled to NOS1, could modulate behavioral responses associated to stress-related disorders and it could be a new target for the development of more effective treatments for affective disorders. (C) 2013 Elsevier B.V. and ECNP. All rights reserved. (AU)

• FAPESP's process: 07/03685-3 - Typical and atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/17281-7 - Involvement of epigenetic mechanisms induced by DNA methylation on stress-induced behavioral consequences and on the expression of genes involved in the neurobiology of depression
• Grantee: Sâmia Regiane Lourenço Joca
• Support Opportunities: Regular Research Grants