Augmentation by citalopram of risperidone-induced monoamine release in rat prefrontal cortex

Mei Huang, Junji Ichiwaka, Zhu Li, Jin Dai, Herbert Y. Meltzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Rationale: Atypical antipsychotics (APDs), e.g. olanzapine and risperidone, have been reported to be effective adjunctive treatment for depression if selective serotonin (5-HT) reuptake inhibitors (SSRIs) alone are ineffective. Objectives and methods: We utilized microdialysis in awake, freely moving rats to study the effect of risperidone in combination with citalopram, an SSRI, on extracellular 5-HT, dopamine (DA), and norepinephrine (NE) efflux in rat medial prefrontal cortex (mPFC). Results: Risperidone (1.0 mg/kg, s.c.), given alone, significantly increased 5-HT, DA, and NE concentrations in the mPFC. Citalopram (10 mg/kg, s.c.), by itself, produced a significant increase in 5-HT levels only. The combination of risperidone and citalopram produced significantly greater increases in efflux of both DA and NE than risperidone alone. However, the effect of this combination on extracellular 5-HT concentrations was not significantly different than that of citalopram alone. The augmentation of DA and NE efflux induced by risperidone plus citalopram could be partially blocked by the selective 5-HT1A antagonist, WAY 100635 (0.2 mg/kg, s.c.). Conclusions: The results suggest that the ability of atypical APDs to augment the therapeutic efficacy of SSRIs in major depression and treatment-resistant depression may be due, at least in part, to potentiation of SSRI-induced increases in cortical DA and NE. The contributions of 5-HT1A receptor stimulation and 5-HT2A and alpha2 adrenergic receptor antagonism to this augmentation are discussed.

Original languageEnglish (US)
Pages (from-to)274-281
Number of pages8
Issue number3
StatePublished - Apr 2006


  • Citalopram
  • Depression
  • Dopamine
  • Microdialysis
  • Norepinephrine
  • Prefrontal cortex
  • Risperidone
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology


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