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 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.
Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, 20-093, Lublin, Poland.
Anna
A
Serefko
Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, 20-093, Lublin, Poland.
Aleksandra
A
Szopa
Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
Aleksandra
A
Wlaź
Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, 20-093, Lublin, Poland.
Sylwia
S
Wośko
Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland.
Piotr
P
Wlaź
Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, 20-093, Lublin, Poland. ewa.poleszak@umlub.pl.
Ewa
E
Poleszak
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D003863:Depression; D004195:Disease Models, Animal; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013315:Stress, Psychological
D000928:Antidepressive Agents; D016194:Receptors, N-Methyl-D-Aspartate; D002110:Caffeine
Antidepressant-like activity; Caffeine; Forced swim test; Mice; NMDA receptor ligands