Fluoxetine increases extracellular dopamine in the prefrontal cortex by a mechanism not dependent on serotonin: a comparison with citalopram

J Neurochem. 1999 Sep;73(3):1051-7. doi: 10.1046/j.1471-4159.1999.0731051.x.

Abstract

Fluoxetine at 10 and 25 mg/kg increased (167 and 205%, respectively) the extracellular dopamine concentration in the prefrontal cortex, whereas 25 (but not 10) mg/kg citalopram raised (216%) dialysate dopamine. No compound modified dialysate dopamine in the nucleus accumbens. The effect of 25 mg/kg of both compounds on cortical extracellular dopamine was not significantly affected by 300 mg/kg p-chlorophenylalanine (PCPA) (fluoxetine, saline, 235%; PCPA, 230%; citalopram, saline, 179%; PCPA, 181%). PCPA depleted tissue and dialysate serotonin by approximately 90 and 50%, respectively, and prevented the effect of fluoxetine and citalopram on dialysate serotonin (fluoxetine, saline, 246%; PCPA, 110%; citalopram, saline, 155%; PCPA, 96%). Citalopram significantly raised extracellular serotonin from 0.1 to 100 microM (251-520%), whereas only 10 and 100 microM increased dialysate dopamine (143-231%). Fluoxetine similarly increased extracellular serotonin (98-336%) and dopamine (117-318%). PCPA significantly reduced basal serotonin and the effects of 100 microM fluoxetine (saline, 272%; PCPA, 203%) and citalopram (saline, 345%; PCPA, 258%) on dialysate serotonin but did not modify their effect on dopamine (fluoxetine, saline, 220%; PCPA, 202%; citalopram, saline, 191%; PCPA, 211%). The results clearly show that the effects of fluoxetine and of high concentrations of citalopram on extracellular dopamine do not depend on their effects on serotonin.

Publication types

  • Comparative Study

MeSH terms

  • Aminopyridines / pharmacology
  • Animals
  • Biogenic Monoamines / metabolism
  • Citalopram / pharmacology*
  • Dopamine / metabolism*
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Fenclonine / pharmacology
  • Fluoxetine / administration & dosage
  • Fluoxetine / pharmacology*
  • Indoles / pharmacology
  • Injections, Intraperitoneal
  • Male
  • Microdialysis
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / pharmacology*

Substances

  • 6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline
  • Aminopyridines
  • Biogenic Monoamines
  • Indoles
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Citalopram
  • Serotonin
  • Fenclonine
  • Dopamine