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Augmentation by escitalopram, but not citalopram or R‐citalopram, of the effects of low‐dose risperidone: Behavioral, biochemical, and electrophysiological evidence
Author(s) -
Marcus Monica M.,
Jardemark Kent,
Malmerfelt Anna,
Gertow Jens,
KonradssonGeuken Åsa,
Svensson Torgny H.
Publication year - 2012
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21510
Subject(s) - citalopram , escitalopram , pharmacology , risperidone , psychology , atypical antipsychotic , dopamine , nmda receptor , antidepressant , chemistry , neuroscience , antipsychotic , medicine , schizophrenia (object oriented programming) , psychiatry , receptor , hippocampus
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. Synapse, 2012. © 2011 Wiley Periodicals, Inc.