| First Author | Gölöncsér F | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 3 | Pages | 109284 |
| PubMed ID | 38444608 | Mgi Jnum | J:351636 |
| Mgi Id | MGI:7611470 | Doi | 10.1016/j.isci.2024.109284 |
| Citation | Goloncser F, et al. (2024) P2X7 receptor inhibition alleviates mania-like behavior independently of interleukin-1beta. iScience 27(3):109284 |
| abstractText | Purinergic dysfunctions are associated with mania and depression pathogenesis. P2X7 receptor (P2X7R) mediates the IL-1beta 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-1beta. Treatment with JNJ-47965567, a P2X7R antagonist, abolished AMPH-induced hyperlocomotion in wild-type and IL-1alpha/beta-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-alpha, 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-1alpha/beta-gene deficiency, attenuated AMPH-induced [(3)H]dopamine release from striatal slices. In wild-type and IL-1alpha/beta-knockout female mice, JNJ-47965567 was also effective in attenuating AMPH-induced hyperlocomotion. This study suggests that AMPH-induced hyperactivity is modulated by P2X7Rs, but not through IL-1beta. |
