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

RATIONALE

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.

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.