title: Enhancement of antidepressant-like activity by joint administration of imipramine and magnesium in the forced swim test: Behavioral and pharmacokinetic studies in mice.
abstract: The effect of joint administration of imipramine (IMI) and magnesium (Mg) on antidepressant-like activity was studied in mice using forced swim test (FST). Mg doses ineffective per se (5 and 10 mg/kg) given jointly with IMI also at ineffective doses (10 and 15 mg/kg) resulted in a potent reduction in the immobility time. Since these combined treatments did not influence locomotor activity, the antidepressant-like activity was not due to non-specific behavioral activation. Moreover, we estimated the effect of joint administration of magnesium and IMI in FST on serum and brain magnesium, IMI and its active metabolite desipramine (DMI) concentrations in mice. Swim stress (mice subjected to FST) increased the magnesium concentration in serum and decreased it in the brain compared to naive animals. Moreover administration of IMI increased (normalized) magnesium brain concentration, without influence on the serum level. Joint administration of IMI and magnesium did not influence magnesium (compared with FST) or IMI and DMI (compared with IMI treatment alone) concentrations in both examined tissues. The present data demonstrated an enhancement of the antidepressant-like effect by joint administration of IMI and magnesium in the FST, and further indicate the particular role of magnesium in the antidepressant action. Since there was no increase in IMI, DMI or magnesium concentration after joint administration of magnesium and IMI, the data suggest that pharmacodynamic rather than pharmacokinetic interaction between magnesium and IMI is accountable for behavioral effect in the FST.
authors.affiliation: Department of Pharmacodynamics, Medical University School, Staszica 8, PL 20-081 Lublin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Poleszak
authors.forename: Piotr
authors.initials: P
authors.lastname: Wlaź
authors.forename: Bernadeta
authors.initials: B
authors.lastname: Szewczyk
authors.forename: Ewa
authors.initials: E
authors.lastname: Kedzierska
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Wyska
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Librowski
authors.forename: Joanna
authors.initials: J
authors.lastname: Szymura-Oleksiak
authors.forename: Sylwia
authors.initials: S
authors.lastname: Fidecka
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pilc
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007099:Imipramine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008274:Magnesium / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013315:Stress, Psychological; D013550:Swimming / Q000502:physiology / Q000523:psychology; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D008274:Magnesium; D007099:Imipramine