title: Caffeine enhances the antidepressant-like activity of common antidepressant drugs in the forced swim test in mice.
abstract: Caffeine is the most widely used behaviorally active drug in the world which exerts its activity on central nervous system through adenosine receptors. Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. The main goal of the present study was to evaluate the influence of caffeine on animals' behavior in forced swim test (FST) as well as the effect of caffeine (5 mg/kg) on the activity of six typical antidepressants, such as imipramine (15 mg/kg), desipramine (10 mg/kg), fluoxetine (5 mg/kg), paroxetine (0.5 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg). Locomotor activity was estimated to verify and exclude false-positive/negative results. In order to assess the influence of caffeine on the levels of antidepressant drugs studied, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. The results showed that caffeine at a dose of 10, 20, and 50 mg/kg exhibited antidepressant activity in the FST, and it was not related to changes in locomotor activity in the animals. Caffeine at a dose of 5 mg/kg potentiated the activity of all antidepressants, and the observed effects were not due to the increase in locomotor activity in the animals. The interactions between caffeine and desipramine, fluoxetine, escitalopram, and reboxetine were exclusively of pharmacodynamic character, because caffeine did not cause any changes in the concentrations of these drugs neither in blood serum nor in brain tissue. As a result of joint administration of caffeine and paroxetine, an increase in the antidepressant drug concentrations in serum was observed. No such change was noticed in the brain tissue. A decrease in the antidepressant drug concentrations in brain was observed in the case of imipramine administered together with caffeine. Therefore, it can be assumed that the interactions caffeine-paroxetine and caffeine-imipramine occur at least in part in the pharmacokinetic phase.
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093, Lublin, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szopa
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093, Lublin, Poland. ewa.poleszak@umlub.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Poleszak
authors.affiliation: Department of Pharmacokinetics and Physical Pharmacy, Collegium Medicum, Jagiellonian University, Medyczna 9, PL 30-688, Kraków, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Wyska
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Serefko
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093, Lublin, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Wośko
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, PL 20-090, Lublin, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Wlaź
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL 20-033, Lublin, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Pieróg
authors.affiliation: Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, PL 20-090, Lublin, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wróbel
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL 20-033, Lublin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wlaź
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D004347:Drug Interactions; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D002110:Caffeine
keywords: Antidepressants; Caffeine; Forced swim test; Mice; Pharmacokinetic study