Effects of imipramine on cytokines panel in the rats serum during the drug treatment and discontinuation. (February 2018)

• Record Type: Journal Article
• Authors: Kuśmider, M.; Faron-Górecka, A.; Pabian, P.; Solich, J.; Szlachta, M.; Kolasa, M.; Żurawek, D.; Wójcikowski, J.; Daniel, W.; Dziedzicka-Wasylewska, M.
• Is Part Of: Neurochemistry international. Volume 113(2017)
• Page Start: 85
• Page End: 91
• Publication Date: 2018-02
• Subjects: Time dependent sensitization -- Antidepressant discontinuation syndrome -- Antidepressants -- Imipramine -- Cytokines -- Rat serum; ADS antidepressant discontinuation syndrome -- ADs antidepressants -- DMI desipramine -- ECS electroconvulsive shock -- FST forced swim test -- IMI imipramine -- SNRIs selective norepinephrine reuptake inhibitors -- SSRIs selective serotonin reuptake inhibitors -- TCA tricyclic antidepressants -- TDS time dependent sensitization; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2017.11.016
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Time dependent sensitization (TDS) - phenomenon described originally by Chiodo and Antelman (1980) in context of dopamine receptors, refers to cascade of events that continue to develop in the organism, after the initiating stimulus is no longer available. Treatment could be recognized as such a initiating stimulus (in case of depression, example of electroconvulsive therapy would be obvious, but some aspects of pharmacotherapy too). The process leads to improvement, but, on the other hand, phenomena of kindling in recurrent depression is well known (more relapses and therapies make heavier and longer lasting subsequent episodes). Hence our interest in delayed effects of treatment. Here we report alterations in rat immune system after Imipramine (IMI) treatment cessation. Wistar male rats were treated with IMI (10 mg/kg i.p. in 2 ml/kg of saline) repeatedly for 21 days or once - on the last day of drug administration period. Then the 3 weeks discontinuation phase begun, during which, at certain time points (3 h, 72 h, 7days, 21days) the trunk blood was collected. Tissue concentrations of IMI and its metabolite desipramine (DMI), as well as ACTH and various cytokines were measured. The IMI and DMI was detectable only 3 h after the last i.p. injection of the drug. Ever since the second time point (72 h of discontinuation) the levels of either compound were below detection threshold.There was no significant changes in ACTH levels between rat groups, although IMI seemed to attenuate alterations of the hormone level comparing to control groups. We observed differences between groups regarding certain cytokines at certain time points. Namely: at 72 h of discontinuation IL-2 and IL-4 were elevated in sera of rats treated with IMI acutely; at 7d of discontinuation levels of IL-1α, IL-5, IL-10 and IL-12 were affected in both acutely and chronically treated animals. Presented data support, regarding some cytokines in serum, the TDS theory. Furthermore they refer to important aspect of antidepressants (ADs) action – antidepressant discontinuation syndrome (ADS). The most frequently, ADS has been described in context of ADs-disrupted monoamine homeostasis. Here, the other principle (i.e. immunomodulation) of the syndrome is proposed. Graphical abstract: Highlights: Imipramine and its metabolite desipramine are undetectable in rat serum since 72 h after last injection. However absent in blood, imipramine affects the levels of several cytokines in rat serum in time dependent manner. Three weeks after chronic imipramine treatment cessation, immune state of rats, regarding Th1/Th2 shift, persists affected.