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Effect of Monoamine Reuptake Inhibitors on Seizures in DBA/1 Mice
Author(s) -
Ahamed Hassan A.,
Kim Yu Jaung,
Bravo Eduardo,
Richerson George B.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.869.11
Subject(s) - escitalopram , fluoxetine , serotonin reuptake inhibitor , serotonin , reuptake inhibitor , pharmacology , epilepsy , anesthesia , saline , medicine , dosing , tonic (physiology) , psychology , antidepressant , psychiatry , hippocampus , receptor
Background DBA/1 mice suffer from audiogenic seizures that lead to wild running, clonic seizures, tonic hind‐limb extension, and eventually seizure induced respiratory arrest (S‐IRA). The use of the selective serotonin reuptake inhibitor (SSRI) fluoxetine has been shown to prevent DBA/1 mice from having S‐IRA and tonic seizures. In the present study we use fluoxetine and the more selective agent escitalopram to determine the role serotonin reuptake plays in seizure protection in DBA/1 mice. Hypothesis High doses of fluoxetine and escitalopram have the ability to completely protect DBA/1 mice from audiogenic seizures. Methods At postnatal day 21 – 24, DBA/1 mice were subjected to audiogenic seizure priming for 3 – 5 days in order to induce ~100% seizure susceptibility. After they were primed, mice were subjected to a drug dosing scheme that consisted of 0 (vehicle), 1, 3, 10, 30 or 100 mg/kg of fluoxetine in a 10% DMSO and saline solution or escitalopram in a saline solution – at the same doses. Mice were then subjected to an audiogenic stimulus (≥106 dB) 30 minutes after drug injection. The stimulus was given for 60 seconds and mice were monitored for convulsions and S‐IRA. For those mice that developed S‐IRA, a mini‐ventilator was used to resuscitate them. If a mouse survived, it was given a week for the drug to clear, then randomized to another dosing group. Results At 100 mg/kg of fluoxetine, DBA/1 mice were completely protected from audiogenic seizures (n = 6 of 6). These mice displayed no evidence of seizures. It was found that all other doses were unable to protect mice from seizures and S‐IRA, except for one mouse at 1 mg/kg (n = 29 of 30). Some DBA/1 mice that received 100 mg/kg as their first dose and allowed to live, developed spontaneous seizures and eventually died 4 – 6 days after injection (n = 2 of 2). At 100 mg/kg of escitalopram, there was a lower success rate relative to fluoxetine; at this dose, escitalopram completely protected some mice (n = 2 of 6), blocked tonic‐clonic seizures (n = 1 of 6), and had no effect on tonic‐clonic + S‐IRA (n = 3 of 6). At lower doses, escitalopram was completely ineffective at stopping seizures and always led to tonic‐clonic seizures + S‐IRA (n = 20 of 20). Conclusions DBA/1 mice were protected from audiogenic seizures at 100 mg/kg of fluoxetine. Escitalopram, does not have as strong of an anticonvulsive effect suggesting that fluoxetine may have off‐target effects that are responsible for its more powerful anticonvulsive properties. It was seen, however, that in some cases DBA/1 mice developed spontaneous seizures after exposure to a high dose of fluoxetine. Support or Funding Information Supported by a STRIDE fellowship from the American Physiological Society and a grant from the National Heart, Lung and Blood Institute.