Synergistic antidepressant-like effect of the joint administration of caffeine and NMDA receptor ligands in the forced swim test in mice

The optimal treatment of depressed patients remains one of the most important challenges concerning depression. The identification of the best treatment strategies and development of new, safer, and more effective agents are crucial. The glutamatergic system seems to be a promising drug target, and...

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Bibliographic Details
Published in:Journal of Neural Transmission 2016-04, Vol.123 (4), p.463-472
Main Authors: Serefko, Anna, Szopa, Aleksandra, Wlaź, Aleksandra, Wośko, Sylwia, Wlaź, Piotr, Poleszak, Ewa
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents - pharmacology
Caffeine - pharmacology
Depression
Disease Models, Animal
Medicine
Medicine & Public Health
Mice
Motor Activity - drug effects
Neurology
Neurosciences
Original
Original Article
Psychiatry
Receptors, N-Methyl-D-Aspartate - agonists
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Stress, Psychological
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Summary:The optimal treatment of depressed patients remains one of the most important challenges concerning depression. The identification of the best treatment strategies and development of new, safer, and more effective agents are crucial. The glutamatergic system seems to be a promising drug target, and consequently the use of the NMDA receptor ligands, particularly in co-administration with other substances exerting the antidepressant activity, has emerged among the new ideas. The objective of this study was to examine the effect of caffeine on the performance of mice treated with various NMDA modulators in the forced swim test. We demonstrated a significant interaction between caffeine (5 mg/kg) and the following NMDA receptor ligands: MK-801 (an antagonist binding in the ion channel, 0.05 mg/kg), CGP 37849 (an antagonist of the glutamate site, 0.312 mg/kg), L-701,324 (an antagonist of the glycine site, 1 mg/kg), and d -cycloserine (a high-efficacy partial agonist of the glycine site, 2.5 mg/kg), while the interaction between caffeine and the inorganic modulators, i.e., Zn 2+ (2.5 mg/kg) and Mg 2+ (10 mg/kg), was not considered as significant. Based on the obtained results, the simultaneous blockage of the adenosine and NMDA receptors may be a promising target in the development of new antidepressants.
ISSN:0300-9564
1435-1463
DOI:10.1007/s00702-015-1467-4