br Galanin in depression A major impediment in

Galanin in depression A major impediment in depression research is the lack of validated animals´ models. Animals not only lack consciousness of self, self-reflection and consideration of others but also hallmarks of the disorder such as depressed mood, low self-esteem or suicidal intent are hardly accessible in non-human (Deussing, 2006). However, depression, as other mental disorders, constitutes of intermediate or so-called endophenotypes that can be reproduced independently and evaluated in animals, including physiological, endocrinological and neuroanatomical alterations as well as behavioural traits. Numerous behavioural paradigms have been established to elucidate face and construct validity of depression models, including antidepressant-screening test (Deussing, 2006). The forced swimming test (FST), the most used paradigm to assess depression- and antidepressant-like behaviour, also known as the ‘behavioural despair’ test, was developed by Porsolt et al. (1977) as a rodent model for predicting the clinical efficacy of antidepressant drugs (Bogdanova et al., 2013). The FST takes advantage of the observation that rodents, following initial escape-oriented movements, rapidly adopt a characteristic immobile posture in an inescapable cylinder filled with water. In this paradigm, immobility is interpreted as a passive stress-coping strategy or depression-like behaviour (behavioural despair) (Deussing, 2006). Fuxe's Laboratory, around nineties, reported the first evidence of the involvement of GAL in depression. In animal models, GAL administered into the lateral ventricle (i.c.v.) reduced serotonin (5-HT) metabolism in ventral limbic cortex, hippocampal formation, and fronto-parietal cortex probably via direct inhibitory actions on dorsal raphe (DR) 5-HT nerve bradykinin receptor antagonist reducing their firing rates (Fuxe et al., 1988b). These results suggested based on the 5-HT hypothesis of depression that GAL, may contribute to depression by reducing firing in the ascending 5-HT neurons (Fuxe et al., 1988b). GAL in the rat ventral tegmental area (VTA) induced in a dose-dependent manner an increased in immobility time in the FST (Weiss et al., 1998), an effect that was blocked by the coinfusion of the GAL receptor antagonist M35. I.c.v. GAL also resulted in an increase of immobility time in FST confirming that GAL may induce depression-like phenotype (Kuteeva et al., 2007). In the rat, intraperitoneal injection of galnon or galmic, GAL receptor agonists, reduced immobility time in the rat FST, indicating an antidepressant-like effect of systemically GAL receptor agonists (Bartfai et al., 2004, Lu et al., 2005) (Table 1). The role of GAL in depression-like behaviour has been analysed in genetically modified mice. Mice over-expressing GAL under the platelet-derived growth factor-B promoter (GalOE-P) displayed an increased immobility in the FST, suggesting a depression-like behaviour (Kuteeva et al., 2005, Kuteeva et al., 2008). However, Holmes et al. (2005) (Holmes et al., 2005) failed to show such alterations in GAL over-expressing mice under the dopamine-β-hydroxylase promoter (GalOE-D) and GAL1 receptor knockout (KO) mice (Table 1). Importantly, GalOE-P but not GalOE-D mice showed an augmentation of hippocampal noradrenaline (NA) and 5-HT release probably indicating that the mechanisms underlying the increase of immobility in GalOE-P can be related to modulation of NA and 5-HT transmission. In a genetic rat model of depression, the Flinder sensitive line, which displays a high immobility in FST, an up-regulation of the GAL receptor binding sites, is found in the DR, and reduces GAL fiber density in the hippocampus and hypothalamus. The results indicate that enhancement of GAL receptors function in the DR rich in 5-HT neurons could be a mechanism involved in the production of depressive-like activity in this animal model of depression (Bellido et al., 2002).
Galanin(1–15) in depression In the FST, i.c.v. GAL(1–15) 3nmol significantly increased the immobility time and decreased the time of climbing by 44% and 46% respectively. In addition, this effect was shown with the administration of GAL(1–15) 6nmol (Millon et al., 2015). The same pattern of response was observed in the TST, GAL(1–15) at the dose of 3nmol also significantly increased the immobility behaviour recorded during the 6min of testing (Millon et al., 2015) (Table 1).