Augmentation by escitalopram, but not citalopram or R-citalopram, of the effects of low-dose risperidone: behavioral, biochemical, and electrophysiological evidence.

Abstract

Antidepressant drugs are frequently used to treat affective symptoms in schizophrenia. We have recently shown that escitalopram, but not citalopram or R-citalopram, increases firing rate and burst firing of midbrain dopamine neurons, potentiates cortical N-methyl-D-aspartate (NMDA) receptor-mediated transmission and enhances cognition, effects that might influence the outcome of concomitant antipsychotic medication. Here, we studied, in rats, the behavioral and neurobiological effects of adding escitalopram, citalopram, or R-citalopram to the second-generation antipsychotic drug risperidone. We examined antipsychotic efficacy using the conditioned avoidance response (CAR) test, extrapyramidal side effect (EPS) liability using a catalepsy test, dopamine outflow in the medial prefrontal cortex (mPFC) and nucleus accumbens using in vivo microdialysis in freely moving animals, and NMDA receptor-mediated transmission in the mPFC using intracellular electrophysiological recording in vitro. Only escitalopram (5 mg/kg), but not citalopram (10 mg/kg), or R-citalopram (10 mg/kg), dramatically enhanced the antipsychotic-like effect of a low dose of risperidone (0.25 mg/kg), without increasing catalepsy. Given alone, escitalopram, but not citalopram or R-citalopram, markedly enhanced both cortical dopamine output and NMDA receptor-mediated transmission. Addition of escitalopram and to some extent R-citalopram, but not citalopram, significantly enhanced both cortical dopamine output and cortical NMDA receptor-mediated transmission induced by a suboptimal dose/concentration of risperidone. These results suggest that adjunct treatment with escitalopram, but not citalopram, may enhance the effect of a subtherapeutic dose of risperidone on positive, negative, cognitive, and depressive symptoms in schizophrenia, yet without increased EPS liability.

• Authors: Monica M Marcus, Kent Jardemark, Anna Malmerfelt, Jens Gertow, Asa Konradsson-Geuken, Torgny H Svensson
• Journal: Synapse (New York, N.Y.) (Synapse) Vol. 66 Issue 4 Pg. 277-90 (Apr 2012) ISSN: 1098-2396 [Electronic] United States
• PMID: 22121030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• Antipsychotic Agents
• Serotonin Uptake Inhibitors
• Citalopram
• Risperidone
• Dopamine

Topics

• Animals
• Antipsychotic Agents (administration & dosage)
• Avoidance Learning (drug effects)
• Behavior, Animal (drug effects)
• Brain (drug effects, metabolism)
• Chromatography, High Pressure Liquid
• Citalopram (administration & dosage)
• Dopamine (metabolism)
• Drug Synergism
• Drug Therapy, Combination
• Electrophysiological Phenomena (drug effects)
• Male
• Microdialysis
• Patch-Clamp Techniques
• Rats
• Rats, Wistar
• Risperidone (administration & dosage)
• Selective Serotonin Reuptake Inhibitors (administration & dosage)