TY - JOUR
T1 - Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats
AU - Mørk, Arne
AU - Montezinho, Liliana P.
AU - Miller, Silke
AU - Trippodi-Murphy, Crista
AU - Plath, Niels
AU - Li, Yan
AU - Gulinello, Maria
AU - Sanchez, Connie
N1 - Funding Information:
Liliana C. P. Montezinho was supported by a grant ( SFRH/BPD/18389/2004 ) from the Fundação para a Ciência e Tecnologia (F.C.T.), Portugal . The authors would like to thank Anette Frederiksen and Nina Guldhammer for their skilful technical assistance with the microdialysis studies. Moreover, the authors would like to thank Dr. Huailing Zhong for his very valuable and competent assistance with writing the manuscript, and Dr. David Simpson for helpful insights and comments.
PY - 2013/4
Y1 - 2013/4
N2 - The serotonergic system plays an important role in cognitive functions via various 5-HT receptors. Vortioxetine (Lu AA21004) in development as a novel multimodal antidepressant is a 5-HT3, 5-HT7 and 5-HT 1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (5-HTT) inhibitor in vitro. Preclinical studies suggest that 5-HT3 and 5-HT7 receptor antagonism as well as 5-HT1A receptor agonism may have a positive impact on cognitive functions including memory. Thus vortioxetine may potentially enhance memory. We investigated preclinical effects of vortioxetine (1-10 mg/kg administered subcutaneously [s.c.]) on memory in behavioral tests, and on cortical neurotransmitter levels considered important in rat memory function. Contextual fear conditioning and novel object recognition tests were applied to assess memory in rats. Microdialysis studies were conducted to measure extracellular neurotransmitter levels in the rat medial prefrontal cortex. Vortioxetine administered 1 h before or immediately after acquisition of contextual fear conditioning led to an increase in freezing time during the retention test. This mnemonic effect was not related to changes in pain sensitivity as measured in the hotplate test. Rats treated with vortioxetine 1 h before training spent more time exploring the novel object in the novel object recognition test. In microdialysis studies of the rat medial prefrontal cortex, vortioxetine increased extracellular levels of acetylcholine and histamine. In conclusion, vortioxetine enhanced contextual and episodic memory in rat behavioral models. Further demonstration of its potential effect on memory functions in clinical settings is warranted.
AB - The serotonergic system plays an important role in cognitive functions via various 5-HT receptors. Vortioxetine (Lu AA21004) in development as a novel multimodal antidepressant is a 5-HT3, 5-HT7 and 5-HT 1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (5-HTT) inhibitor in vitro. Preclinical studies suggest that 5-HT3 and 5-HT7 receptor antagonism as well as 5-HT1A receptor agonism may have a positive impact on cognitive functions including memory. Thus vortioxetine may potentially enhance memory. We investigated preclinical effects of vortioxetine (1-10 mg/kg administered subcutaneously [s.c.]) on memory in behavioral tests, and on cortical neurotransmitter levels considered important in rat memory function. Contextual fear conditioning and novel object recognition tests were applied to assess memory in rats. Microdialysis studies were conducted to measure extracellular neurotransmitter levels in the rat medial prefrontal cortex. Vortioxetine administered 1 h before or immediately after acquisition of contextual fear conditioning led to an increase in freezing time during the retention test. This mnemonic effect was not related to changes in pain sensitivity as measured in the hotplate test. Rats treated with vortioxetine 1 h before training spent more time exploring the novel object in the novel object recognition test. In microdialysis studies of the rat medial prefrontal cortex, vortioxetine increased extracellular levels of acetylcholine and histamine. In conclusion, vortioxetine enhanced contextual and episodic memory in rat behavioral models. Further demonstration of its potential effect on memory functions in clinical settings is warranted.
KW - Acetylcholine
KW - Cognitive dysfunction
KW - Memory
KW - Multimodal
KW - Serotonin
KW - Vortioxetine
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U2 - 10.1016/j.pbb.2013.01.019
DO - 10.1016/j.pbb.2013.01.019
M3 - Article
C2 - 23380522
AN - SCOPUS:84874182123
SN - 0091-3057
VL - 105
SP - 41
EP - 50
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
ER -