title: 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: Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, S-17177 Stockholm, Sweden. monica.marcus@ki.se
authors: Monica M
authors: MM
authors: Marcus
authors: Kent
authors: K
authors: Jardemark
authors: Anna
authors: A
authors: Malmerfelt
authors: Jens
authors: J
authors: Gertow
authors: Asa
authors: A
authors: Konradsson-Geuken
authors: Torgny H
authors: TH
authors: Svensson
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D055724:Electrophysiological Phenomena / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000008:administration & dosage*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*
chemical_list: D014150:Antipsychotic Agents; D015283:Citalopram; D004298:Dopamine; D018967:Risperidone; D017367:Selective Serotonin Reuptake Inhibitors