Stimulation of P2X7Rs by high level of ATP (hundreds of μM) produces a large transmembrane pores, permeable to large molecular sizes of up to 900 Da, promoting further increase in extracellular ATP release that can lead to activation of caspases and result in cell death.189 P2X7 receptor expression in the CNS could be increased with systemic administration of bacterial lipopolysaccharide (LPS), providing a realistic mechanism similar to systemic infection in the brain.6 Genetic deficiency and pharmacological inhibition of P2X7 receptors have shown to attenuate hyperactivity induced by amphetamine in the model of manic bipolar disorder.190 Mood stabilizer drugs such as lithium and valproate reversed ATP-induced cell death in the hippocampus, an action that is probably mediated by P2X7 receptors.191,192
