P2X7 receptor inhibition alleviates mania-like behavior independently of interleukin-1β.

Purinergic dysfunctions are associated with mania and depression pathogenesis. P2X7 receptor (P2X7R) mediates the IL-1β maturation via NLRP3 inflammasome activation. We tested in a mouse model of the subchronic amphetamine (AMPH)-induced hyperactivity whether P2X7R inhibition alleviated mania-like behavior through IL-1β. Treatment with JNJ-47965567, a P2X7R antagonist, abolished AMPH-induced hyperlocomotion in wild-type and IL-1α/β-knockout male mice. The NLRP3 inhibitor MCC950 failed to reduce AMPH-induced locomotion in WT mice, whereas the IL-1 receptor antagonist anakinra slightly increased it. AMPH increased IL-10, TNF-α, and TBARS levels, but did not influence BDNF levels, serotonin, dopamine, and noradrenaline content in brain tissues in either genotypes. JNJ-47965567 and P2rx7-gene deficiency, but not IL-1α/β-gene deficiency, attenuated AMPH-induced [

Informations de copyright

© 2024 The Authors.

Déclaration de conflit d'intérêts

The authors declare no competing interests.