PhD Scientific Days 2024

Budapest, 9-10 July 2024

Poster Session I - Neurosciences 2.

Effects of Sumatriptan on P2X7 Purinergic Receptor-mediated Signaling in an Amphetamine-induced Acute Mania Mouse Model


Fruzsina Maácz1,2, Flóra Gölöncsér1, Beáta Sperlágh1
1: HUN-REN Institute of Experimental Medicine, Laboratory of Molecular Pharmacology
2: School of PhD Studies, Semmelweis University, Szentágothai János Neuroscience Division

Text of the abstract

Introduction: Acute mania is a phase of bipolar disorder. Symptoms include, among others, elevated mood, overconfidence in abilities, and intense energy. Dysfunction of purinergic signaling plays a role in the pathophysiology of acute mania. The P2X7 receptor (P2X7R) affects neurotransmitter release and mania-like behavior in mouse models and probably regulates serotonergic transmission.
Aim: Our aim is to investigate whether the serotonin 5-HT1A/1B/1D receptor agonist sumatriptan, affects manic behaviour in the studied animal model.
Methods: Our research investigated amphetamine-induced hyperactivity in wild-type (WT) and P2X7R gene knockout (P2X7KO) mice using open-field (OF) test, changes in c-fos expression in the striatum using immunohistochemistry and we measured dopamine and serotonin release from the striatum after amphetamine induction.
Results: In the behavioral assay, sumatriptan and the P2X7R antagonist JNJ47965567 reduced amphetamine-induced hyperlocomotion in WT mice, whereas sumatriptan had no effect in P2X7KO mice. C-fos expression was increased by amphetamine in both WT and P2X7KO mice. C-fos expression was increased by amphetamine in both WT and P2X7KO mice, which was decreased by sumatriptan in WT but not P2X7KO mice. Dopamine and serotonin release was increased by amphetamine in both WT and P2X7KO mice but was lower in P2X7KO mice. This effect was reduced depending on concentration by adding sumatriptan in WT mice. The 5-HT1B/1D receptor antagonist GR127935 had the opposite effect in the behavioral assay and release experiments than sumatriptan.
Conclusion: Our results suggest that sumatriptan inhibits mania-like behavior in mice and that P2X7R plays a role in mediating its modulatory effect. Thus, sumatriptan may be effective not only in the treatment of migraine but also in the treatment of mania.