Seizure prophylaxis in an animal model of epilepsy by dietary fluoxetine supplementation.
Clinical and animal model evidence suggests that selective serotonin reuptake inhibitors (SSRIs) act as anticonvulsants. The present studies tested the possibility that the El mouse model of genetically predisposed/handling-triggered epilepsy would exhibit fewer seizures following SSRI treatment via dietary fluoxetine adulteration. In particular, potential bioenergetic and neural mechanisms for anticonvulsant efficacy of fluoxetine were explored using food intake/body weight monitoring and quantification of brain serotonin transporter protein. El mice consuming a chow diet ad libitum or yoked in quantity to fluoxetine diet intake exhibited seizure incidence of 40% in response to tail-suspension handling, whereas seizures were abolished (0%) among El mice consuming a fluoxetine-adultered diet over 7 days. A 3 day period of fluoxetine administration was insufficient to exert anticonvulsant efficacy and all treatment groups exhibited the same circadian locomotor activity patterns at the time of seizure susceptibility testing. Bioenergetic factors could not account for the anticonvulsant efficacy of fluoxetine since yoked diet controls with matched food intake, body weight change and blood glucose levels exhibited the same 40% seizure incidence as ad libitum chow controls. Importantly, the 7 day period of dietary fluoxetine exposure was effective in selectively reducing cell density in the parietal cortex and increasing serotonin transporter protein content in the nucleus accumbens. Taken together, these results suggest that dietary fluoxetine supplementation abolishes handling-induced seizure susceptibility in El mice via a neural remodeling mechanism independent of energy balance.
Richman
Alyssa
A
Department of Psychology, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, United States.
Heinrichs
Stephen C
SC
D000821:Animal Feed; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005473:Fluoxetine / Q000008:administration & dosage / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease; D006234:Handling, Psychological; D019417:Hindlimb Suspension / Q000009:adverse effects*; D051379:Mice; D008815:Mice, Inbred Strains; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D012646:Self Administration; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*
D000927:Anticonvulsants; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors