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

• Published in: Epilepsia (Copenhagen) Vol. 45; no. 9; pp. 1035 - 1042
• Main Authors: Riazi, Kiarash, Honar, Hooman, Homayoun, Houman, Rashidi, Narges, Dehghani, Mehdi, Sadeghipour, Hamed, Gaskari, Seyed Ali, Dehpour, Ahmad Reza
• Format: Journal Article
• Language: English
• Published: 350 Main Street , Malden , MA 02148 , USA and 9600 Garsington Road , Oxford , OX4 2XG , England Blackwell Science Inc 01.09.2004; Blackwell
• Subjects: Animals; Anticonvulsants - pharmacology; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Convulsants - administration & dosage; Convulsants - pharmacology; Disease Susceptibility; Dose-Response Relationship, Drug; Estrous Cycle - physiology; Estrus cycle; Female; Gonadal Steroid Hormones - physiology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Infusions, Intravenous; Male; Medical sciences; Mice; Morphine; Morphine - pharmacology; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Orchiectomy; Ovariectomy; Pentylenetetrazole; Pharmacology. Drug treatments; Seizure; Seizures - chemically induced; Seizures - prevention & control; Sex differences; Sex Factors; Nervous system diseases; Epilepsy; Rodentia; Sex; Opiates; Morphine; Narcotic analgesic; Cerebral disorder; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Sex differences-Morphine-Pentylenetetrazole- Seizure-Estrus cycle-Mice
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.0013-9580.2004.69903.x

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.