دانلود رایگان مقاله بهبود آگونیست گیرنده CRF2 انتخابی اضطراب و افسردگی

Abstract

The aim of the present study was to investigate the effects of the selective agonists of the corticotropin-releasing factor (CRF) 2 receptor, urocortin 2 (UCN 2) and urocortin 3 (UCN 3), on the anxiety- and depression-like signs induced by acute nicotine withdrawal in mice. In order to do so, male CFLP mice were exposed for 7 days to repeated intraperitoneal (IP) injection with nicotine or saline solution and 1 day of acute withdrawal and then a single intracerebroventricular (ICV) injection with UCN 2, UCN 3 or saline solution. After 30 min the mice were observed in an elevated plus-maze test or a forced swim test, for anxiety- and depression-like behavior. After 5 min of testing, the plasma corticosterone concentration reflecting the activity of the hypothalamic-pituitaryadrenal (HPA) axis was also determined by a chemo-fluorescent method. Half of the animals were treated ICV and evaluated on the 8th day, the other half on the 9th day. On the 8th day, nicotine-treated mice presented signs of anxiolysis and depression, but no significant elevation of the plasma corticosterone concentration. On the 9th day, nicotine-treated mice exhibited signs of anxiety and depression and a significant increase of the plasma corticosterone levels. Central administration of UCN 2 or UCN 3 ameliorated the anxiety- and depression-like state including the hyperactivity of the HPA axis, developed during acute withdrawal following chronic nicotine treatment. The present study suggests that selective CRF2 receptor agonists could be used as a therapy in nicotine addiction.

4.5. Forced swim test

Thirty minutes after the ICV administration, half of the mice (N=36) were evaluated for depression-like behavior in a forced swim test for 5 min. Half of these mice were tested on the 8th day and the other half on the 9th day. The apparatus, described originally by Porsolt et al. (1977), consists of a plexiglass cylinder of 200 mm height and 120 mm diameter, containing 1.5 l of water. Each mouse was dropped individually into the water, maintained at 25 ± 1 °C. The principle of the test is that in such a situation, from which they cannot escape, animals rapidly became immobile, that is, floating in an upright position and making only small movements to keep their heads above water. In parallel, their attempt to escape the cylinder by climbing or swimming may decrease or cease eventually. For 5 min period the following parameters were recorded by an observer sitting at 1 m distance from the center of the plus-maze: 1. the climbing activity (the time that mice spent with climbing the walls, in their attempt to escape the cylinder), 2. the swimming activity (the time that mice spent with swimming in the water, in their attempt to remain at the surface) and 3. the time of immobilization (the time that mice spent in an upright position on the surface with its front paws together). A 5 s period was considered a time unit, therefore the activity and the immobility were expressed in time units.