Central Phoenixin Protective Role on Pentylenetetrazol-Induced Seizures during Various Stages of the Estrous Cycle among Rats

Arch Razi Inst. 2022 Apr 30;77(2):689-695. doi: 10.22092/ARI.2022.357297.2014. eCollection 2022 Apr.

Abstract

It is known that phoenixin-14 (PNX-14) has a mediatory role in reproduction; however, there is no report on the role of the PNX-14 on epilepsy. Therefore, this study aimed to investigate the antiepileptic effects of the PNX-14 on the pentylenetetrazol (PTZ)-induced epilepsy in the stages of the estrous cycle among rats. A total of 168 adult female Wistar rats were randomly divided into seven groups, including control (intracerebroventricular injection was performed with saline), PNX-14 (5 µg), PNX-14 (10 µg), bicuculline (competitive antagonist of GABAA receptors; 5 nmol)+PNX-14 (5 µg), bicuculline (BIC) (5 nmol)+PNX-14 (10 µg), saclofen (competitive antagonist of GABAB receptors; 2.5 µg)+PNX-14 (5 µg), and saclofen (2.5 µg)+PNX-14 (10 µg) in proestrus, estrus, metestrus, and diestrus. Afterward, the control and treatment groups were followed by intraperitoneal administration of 80 mg/kg PTZ. Initiation time of myoclonic seizures (ITMS), initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were monitored and recorded for 30 min. According to the results, PNX-14 alone significantly reduced the SD and seizure mortality in all phases of estrus (P<0.05). The injection of PNX-14 with BIC significantly reduced SD and seizure mortality in all estrus phases (P<0.05). PNX-14 alone increased both ITMS and ITTS in all phases of estrus (P<0.05). Furthermore, the injection of PNX-14 with BIC significantly reduced the effects of the PNX-14 on ITMS and ITTS in all estrus stages (P<0.05). These results showed that the antiepileptic activity of PNX-14 was probably mediated by GABAA receptors, and this effect was more prominent during the luteal phase than the follicular phase.

Keywords: Estrus cycle; Pentylentetrazole; Phoenixin; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / adverse effects
  • Baclofen / adverse effects
  • Bicuculline / adverse effects
  • Estrous Cycle
  • Female
  • Pentylenetetrazole* / adverse effects
  • Rats
  • Rats, Wistar
  • Seizures* / chemically induced
  • Seizures* / drug therapy
  • Seizures* / prevention & control

Substances

  • Anticonvulsants
  • Baclofen
  • Bicuculline
  • Pentylenetetrazole
  • saclofen