Augmentation by citalopram of risperidone-induced monoamine release in rat prefrontal cortex.
BACKGROUND
A typical 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.


OBJECTIVE
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.
Huang
Mei
M
Division of Psychopharmacology, Departments of Psychiatry and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Ichiwaka
Junji
J
Li
Zhu
Z
Dai
Jin
J
Meltzer
Herbert Y
HY
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015283:Citalopram / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D014150:Antipsychotic Agents; D015283:Citalopram; D004298:Dopamine; D009638:Norepinephrine; D010879:Piperazines; D011725:Pyridines; D018967:Risperidone; D012701:Serotonin; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide