Imipramine attenuates behavioral, immune and neuroendocrine alterations in a rat chronic mild stress model

Katarzyna Curzytek1, Weronika Duda1, Piotr Gruca2, Marta Kubera1, Agnieszka Basta-Kaim1, Boguslawa Budziszewska1, Monika Leskiewicz1, Ewa Szczesny1, Jan Detka1, Wojciech Nowak3, Michael Maes4, Wladyslaw Lason1, Magdalena Regulska1. 1Institute of Pharmacology Polish Academy of Sciences, Department of Experimental Neuroendocrinology, Smetna Street, 31-343 Krakow, Poland, 2Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, Smetna Street, 31-343 Krakow, Poland, 3Jagiellonian University, Medical College, Sw. Anny 12, 31-008 Krakow, Poland, 4Maes Clinic & TRIA, Piyavate Hospital, 10310 Bangkok, Thailand

Evidence suggests an association between depressive disorders and immune and neuroendocrine alterations. A rat model of chronic mild stress (CMS) provide a relatively realistic animal model of the decreased response to reward (anhedonia) that characterizes depression. The aim of the present study was explore the antidepressant effects of imipramine on immunological parameters involved in the CMS model of depression in male Wistar rats. Statistical differences were determined by the analysis of the variance ANOVA followed by Newman-Keuls’ test (behavioral study) or Fischer post hoc analysis (neuroimmunoendocrine study). Chronic mild stress, applied for three weeks, caused a significant decrease of the consumption of 1% sucrose solution. In animal treated with saline, the effect was maintained through the whole experiment [F(6,98) = 107,82; p<0.001]. Imipramine (10 mg/kg, ip) had no significant effect on sucrose consumption in non-stressed animals. However, the drug caused a gradual increase in the sucrose intake in stressed animals, resulting in a complete reversal of the effect of the stress by the end of the six-week treatment period treatment effect. The important observation in the present study was that sucrose intake reduction induced by CMS was related to specific alterations in immune and neuroendocrine parameters in male Wistar rats and that they were reversed with chronic imipramine administration. Our present results showed among others that imipramine increased ability of splenocytes to produce interleukin 10 (p<0.01) and prevent the CMS-induced increase in interferon gamma level (p<0.01) and decrease in ciliary neurotrophic factor (p<0.05), indicating that the effects of the imipramine on cytokine biosynthesis may contribute to its antidepressant properties. In conclusion it is suggested that the therapeutic efficacy of antidepressants may be related to their negative immunoregulatory effects.

This work was supported by grant POIG.01.01.02-12-004/09-00