Chronic treatment with citalopram facilitates the effect of a challenge dose on cortical serotonin output: role of presynaptic 5-HT1A receptors

Eur J Pharmacol. 1994 Aug 1;260(2-3):243-6. doi: 10.1016/0014-2999(94)90344-1.

Abstract

In animals given citalopram (10 mg/kg) twice daily for 14 days a further dose of 1 mg/kg, administered 24 h after the last dose, markedly increased cortical dialysate serotonin (5-hydroxytryptamine, 5-HT), but had no effect in control animals. The effect on dialysate 5-HT in the dorsal raphe was not increased by the chronic treatment. At 25 micrograms/kg, 8-hydroxy-2-(di-n-propylamino)tetralin, an agonist at 5-HT1A receptors, reduced cortical 5-HT output in controls but not in animals treated chronically with citalopram whereas 50 micrograms/kg reduced 5-HT output in both groups. These findings suggest that somatodendritic 5-HT1A receptors are desensitized after chronic treatment with citalopram and this results in facilitation of its effect on cortical dialysate 5-HT. These results also agree with the concept that the effect of 5-HT re-uptake inhibitors on increasing 5-HT output in the frontal cortex is attenuated by their simultaneous ability to activate somatodendritic 5-HT1A receptors via an increase of endogenous 5-HT in the raphe region.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Citalopram / administration & dosage
  • Citalopram / pharmacology*
  • Dialysis
  • Male
  • Raphe Nuclei / drug effects*
  • Raphe Nuclei / metabolism
  • Raphe Nuclei / pathology
  • Raphe Nuclei / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism*
  • Serotonin Uptake Inhibitors / pharmacology

Substances

  • Receptors, Serotonin
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin