Fluoxetine inhibits cortical spreading depression in weaned and adult rats suckled under favorable and unfavorable lactation conditions.
Wistar rats (n = 58) were injected subcutaneously during the lactation period with fluoxetine (5, 10, 20 or 40 mg/kg/day) and cortical spreading depression (SD) was recorded immediately after weaning (25-30 days of life). An additional group (10 mg/kg; n = 8) was SD-recorded at 60-70 days. As compared to the saline-injected (n = 24) or "ingenuous" (n = 16) controls, fluoxetine dose-dependently reduced (P < 0.05) SD-velocities in the young rats by 4, 6, 16 and 15%, respectively, and in adult rats by 13%. In another experiment (26 adult rats), topical cortical application of fluoxetine (5 and 10 mg/ml solutions over the intact dura-mater for 10 min; n = 12 and 14, respectively) dose-dependently reduced SD-velocity (7.6% and 43.3% maximal reductions; P < 0.05). SD-propagation was blocked in 4 out of the 14 W-rats topically treated with the highest fluoxetine concentration (10 mg/ml). This topical fluoxetine effect was reverted after flushing the treated region with saline. In additional, 58 early-malnourished rats, fluoxetine applied during the suckling period (10 mg/kg/day, s.c.) and topically (10 mg/ml) also reduced (P < 0.05) SD-velocities by 18 and 22% for the systemic treatment (young and adult animals, respectively) and by 22.4% for the topical one. The present fluoxetine action supports the hypothesis of an antagonistic serotoninergic influence on SD, as previously suggested in experiments using other serotoninergic drugs. Data also suggest that early malnutrition does not greatly affect fluoxetine effects on SD.
dos Santos
Angela Amâncio
AA
Departamento de Nutrição, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil.
Pinheiro
Patrícia Calado Ferreira
PC
de Lima
Denise Sandrelly Cavalcanti
DS
Ozias
Mirella Gondim
MG
de Oliveira
Manuella Batista
MB
Guimarães
Natália Xavier
NX
Guedes
Rubem Carlos Araújo
RC
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D013181:Cortical Spreading Depression / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000379:methods; D005473:Fluoxetine / Q000494:pharmacology*; D007774:Lactation / Q000502:physiology*; D044342:Malnutrition / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014886:Weaning
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D011189:Potassium Chloride