title: The influence of caffeine on the activity of moclobemide, venlafaxine, bupropion and milnacipran in the forced swim test in mice.
abstract: OBJECTIVE
  Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. It is thus possible to demonstrate the usefulness of caffeine and its derivatives in the treatment of depression. The main goal of the present studywas to evaluate the influence of caffeine (5mg/kg) on the activity of moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg), bupropion (10 mg/kg), and milnacipran (1.25 mg/kg). Moreover, we assessed the influence of caffeine on their serum and brain levels using highperformance liquid chromatography.
  
  
  METHODS
  The experiment was carried out on naïve adult male Albino Swiss mice. Caffeine and tested drugs were administered intraperitoneally. The influence of caffeine on the activity of selected antidepressant drugs was evaluated in forced swim test (FST). Locomotor activity was estimated to verify and exclude false positive/negative results. To assess the influence of caffeine on the levels of studied antidepressant drugs, their concentrations were determined in murine serum and brains using high-performance liquid chromatography.
  
  
  RESULTS
  Caffeine potentiated activity of all antidepressants examined in FST and the observed effects were not due to the increase in locomotor activity in the animals. Only in the case of co-administration of caffeine and milnacipran an increased milnacipran concentration in serum was observed without affecting its concentration in the brain.
  
  
  CONCLUSIONS
  Caffeine potentiates the activity of antidepressant drugs from different chemical groups. The interactions of caffeine with venlafaxine, bupropion and moclobemide occur in pharmacodynamic phase, whereas the interaction of caffeine–milnacipran occurs, at least partially, in pharmacokinetic phase.
authors.affiliation: Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093 Lublin, Poland. Electronic address: ewa.poleszak@umlub.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Poleszak
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 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: Sylwia
authors.initials: S
authors.lastname: Wośko
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 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; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D016642:Bupropion / Q000493:pharmacokinetics / Q000494:pharmacology*; D002110:Caffeine / Q000493:pharmacokinetics / Q000494:pharmacology*; D003511:Cyclohexanols / Q000493:pharmacokinetics / Q000494:pharmacology*; D003521:Cyclopropanes / Q000493:pharmacokinetics / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D008297:Male; D051379:Mice; D000078764:Milnacipran; D020912:Moclobemide / Q000493:pharmacokinetics / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D013550:Swimming; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D003521:Cyclopropanes; D016642:Bupropion; D002110:Caffeine; D000069470:Venlafaxine Hydrochloride; D000078764:Milnacipran; D020912:Moclobemide
keywords: Antidepressant drugs; Caffeine; Forced swim test; Mice; Pharmacokinetic study