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

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• 作者：Vitor S. Pereira ; Plinio C. Casarotto ; Vin铆cius A. Hiroaki-Sato ; Ari ; ra G. Sartim ; Francisco S. Guimar茫es ; S芒mia R.L. Joca
• 关键词：P2 receptor ; PPADS ; Forced swimming test ; Marble burying ; Purinergic system
• 刊名：European Neuropsychopharmacology
• 出版年：December, 2013
• 年：2013
• 卷：23
• 期：12
• 页码：1769-1778
• 全文大小：1098 K

文摘

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 NO_x 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.