Sex and Estrus Cycle Differences in the Modulatory Effects of Morphine on Seizure Susceptibility in Mice

Abstract

Summary:Purpose: To evaluate the effects of sex and estrus cycle on biphasic anticonvulsant and proconvulsant modulation of seizure threshold by morphine.Methods: The threshold for the clonic seizures (CST) induced by acute intravenous administration of γ -aminobutyric acid (GABA)-antagonist pentylenetetrazole (PTZ) was assessed in male and female mice. Estrus cycle was assessed by vaginal smears. The effect of removing circulating sex hormones was assessed by gonadectomy.Results: At baseline, diestrus females had a higher CST compared with males and estrus females. Morphine at lower doses (0.5-3 mg/kg) had a significant anticonvulsant effect in males and estrus females compared with that in vehicle-treated controls, whereas female mice in diestrus phase showed a relative subsensitivity to this effect. Morphine at higher doses (30 and 60 mg/kg) significantly decreased CST in males and diestrus females, with less relative effect in estrus mice. In both phases, morphine exerted stronger effects in males compared with females. Ovariectomy brought the baseline CST to the male level and resulted in significant expression of both phases of morphine effect but did not abolish the sex difference in responsiveness to morphine.Conclusions: The biphasic modulation of seizure threshold is subject to both constitutive sex differences in sensitivity to morphine and hormonal fluctuations during the estrus cycle.

Anti-convulsant Effect and Mechanism of Astragalus mongholicus Extract In Vitro and In Vivo: Protection Against Oxidative Damage and Mitochondrial Dysfunction

“…However, it did not render a significant anticonvulsant effect in the MES model. Meanwhile, PTZ is a transmission blocker of c-aminobutyric acid [41]. Also, the scavenging effect of AM root extract on lipid and hydroxyl radicals indicates that the extract has an effect on the GABAergic system (Fig.…”

Anticonvulsant Activity of Otostegia persica (Burm.) Boiss

“…C l o n i c s e i z u r e w a s i n d u c e d b y γ-aminobutyric acid (GABA) transmission blocker PTZ (Riazi et al, 2004). Regarding the possible contribution of GABAergic system in the anticonvulsant activity of the extrat, flumazenil, a benzodiazepine receptor antagonist, was used (File and Pellow, 1986).…”

Anticonvulsant effects of aerial parts of Passiflora incarnata extract in mice: involvement of benzodiazepine and opioid receptors

“…Clonic seizure was induced by γ-aminobutyric acid (GABA) transmission blocker PTZ [34]. Regarding the possible contribution of GABAergic system in the anticonvulsant activity of Pasipay, flumazenil, a benzodiazepine receptor antagonist, was used [24].…”