《生物制药 论文1》由会员分享，可在线阅读，更多相关《生物制药 论文1（7页珍藏版）》请在金锄头文库上搜索。
1、Memory facilitating effects of agomelatine in the novel object recognition memory paradigm in the ratValrie Bertaina-Angladea, Christophe Drieu-La-Rochellea, Elisabeth Mocarb, Laure SeguinbaBiotrial, Department of Preclinical Pharmacology, 7-9 rue J-L Bertrand, 35000 Rennes, France bInstitut de Rech
2、erches Internationales Servier, 6 place des Pliades, 92415 Courbevoie, Francea b s t r a c ta r t i c l ei n f oArticle history: Received 27 September 2010 Received in revised form 4 February 2011 Accepted 14 February 2011 Available online xxxxKeywords: Agomelatine Memory facilitating effects Novel
3、object recognition task Melatonin SB 242,084 RatThe aim of the present study was to evaluate the effects of agomelatine, an antidepressant with melatonergic agonist and 5-HT2Cantagonist properties, in the rat novel object recognition (NOR) task, a model of short- term episodic memory. To assess the
4、potential involvement of its chronobiotic activity, single intraperitoneal administration of agomelatine and NOR testing were performed either in the evening or in the morning. In both conditions, using a 24 h retention interval, vehicle-treated rats did not discriminate between the novel and the fa
5、miliar object (recognition index was not different from chance performance) while object memory performance of rats treated with agomelatine either in the evening (10 and 40 mg/kg) or in the morning (2.5,10, and 40 mg/kg) was significantly improved. Moreover, the selective 5-HT2Cantagonist SB 242,08
6、4 (0.63, 2.5, and 10 mg/kg) and melatonin (2.5, 10, and 40 mg/kg) displayed also memory facilitating effects in both administration conditions. Finally, thioperamide used as positive reference compound to validate the experimental conditions, demonstrated a memory facilitating effect. In conclusion,
7、 agomelatine was shown to possess memory facilitating effects in the rat NOR task and both melatonergic agonist and 5-HT2Cantagonist properties could be involved in these effects. 2011 Elsevier Inc. All rights reserved.1. IntroductionAgomelatine is a novel antidepressant acting as a potent agonist o
8、f melatonergic MT1 and MT2 receptors (Ying et al., 1996; Yous et al., 1992) and an antagonist of the 5-HT2Creceptors (Millan et al., 2003).Agomelatine has demonstrated a clear efficacy as an antidepressant in clinical trials (Kennedy and Emsey, 2006; Lo et al., 2002; Olie and Kasper, 2007; Kennedy,
9、2009; Kennedy and Rizvi, 2010) with fewer side-effects than more classical antidepressants (Kasper and Hamon, 2009; Kennedy and Rizvi, 2010). The chronobiotic activity of agomelatine may contribute to itsefficacy in treating patients with major depressive disorder (MDD), the disruption of internal c
10、ircadian rhythms being one important feature of depression (Wehr and Wirz-Justice, 1982). Indeed, in preclinical studies, agomelatine is able to re-synchronise disrupted circadian rhythms (Armstrong et al., 1993; Martinet et al., 1996; Redman et al., 1995; Van Reeth et al., 1997). After chronic trea
11、tment, agomelatine dose-dependently restored the phase shifting response to a dark pulse (Van Reeth et al., 2001) and accelerated the resynchronization of the rhythm to new lightdark cycle in aged hamsters by 25% (Weibel et al., 2000). The re-entraining activity ofagomelatine is linked to its recept
12、or profile, and a clear relationbetween plasma agomelatine concentration and entrainment has been demonstrated (Martinet et al., 1996). In preclinical studies, agomelatine has been shown to display antidepressant and anxiolytic properties in different experimental models: antidepressant-like effects
13、 of agomelatine have been shown in the forced swimming test (Bourin et al., 2004), the chronic mild stress model (Papp et al., 2003), the learned helplessness model (Bertaina- Anglade et al., 2006a) and a transgenic mouse model with low glucocorticoid receptor function (Barden et al., 2005); anxioly
14、tic-like effects of agomelatine have been described in rats subjected to the socialinteraction test and the Vogel conflict procedure (Millan et al., 2005), the elevated plus-maze test (Papp et al., 2006) and the social defeat model (Tuma et al., 2005). Preclinical (Henningsen et al., 2009; Kalueff a
15、nd Murphy, 2007) and clinical (Baune et al., 2008; Hammar and Ardal, 2009) data suggest that depressive disorders are often associated with cognitive impairment in different cognitive domains such as executive function, working memory and attention. In order to evaluate the effects of agomelatine on
16、 memory, we initially tested the compound in a reference memory model, the T maze leftright spatial discrimination test. In this model, a single administration of agomelatine (1 and 10 mg/kg) improved discrimination performance of the mice, the effect being more intense when agomelatine was administered in the evening compared to a morning administration (Jaffard et al., 1993). Besides, recent data suggests that, following chronic treatment, agomelatine (10 mg/kg) is able to reverse a
