Evaluation of the role of NMDA receptor function in antidepressant-like activity. A new study with citalopram and fluoxetine in the forced swim test in mice.
BACKGROUND
The NMDA/glutamate receptors are involved in the mechanism of antidepressant activity.


METHODS
The present study was designed to investigate the effect of NMDA receptor ligands (agonists and antagonists of glutamate sites) on the antidepressant-like activity of selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, in the forced swim test in mice.


RESULTS
The antidepressant activity (reduction in immobility time) of citalopram but not of fluoxetine was antagonized by N-methyl-D-aspartate acid and enhanced by CGP37849 (antagonist of the NMDA receptor).


CONCLUSIONS
The present literature data indicate that the antidepressant-like activity of conventional antidepressants is generally affected by the NMDA receptor, although by modulation from different sites of the complex. Thus, it supports the issue of the ability of NMDA receptor antagonists to enhance the antidepressant action in human depression.
Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland; Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Małgorzata
M
Wolak
Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland; Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Agata
A
Siwek
Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Bernadeta
B
Szewczyk
Department of Applied Pharmacy, Medical University of Lublin, Lublin, Poland.
Ewa
E
Poleszak
Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Beata
B
Bystrowska
Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Andrzej
A
Moniczewski
Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Anita
A
Rutkowska
Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland; Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Katarzyna
K
Młyniec
Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland; Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: nowak@if-pan.krakow.pl.
Gabriel
G
Nowak
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005473:Fluoxetine / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013550:Swimming / Q000523:psychology
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D016194:Receptors, N-Methyl-D-Aspartate; D005473:Fluoxetine; D015283:Citalopram; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D015763:2-Amino-5-phosphonovalerate
CGP 37849; Citalopram; Fluoxetine; Forced swim test; NMDA