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

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          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 12.5mg/kg showed reduced immobility time in the forced swimming test (FST) similarly to the prototype antidepressant imipramine (30mg/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.

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          Author and article information

          Journal
          Eur Neuropsychopharmacol
          European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
          Elsevier BV
          1873-7862
          0924-977X
          Dec 2013
          : 23
          : 12
          Affiliations
          [1 ] Department of Pharmacology, School of Medicine, Campus USP, Ribeirão Preto, SP 14049-900, Brazil.
          Article
          S0924-977X(13)00047-3
          10.1016/j.euroneuro.2013.01.008
          23434291
          53888a21-f884-46cb-be4a-cbc8d08120c2
          Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.
          History

          Forced swimming test,Marble burying,P2 receptor,PPADS,Purinergic system

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