These results may be explained by increased levels of hippocampal BDNF and 5-HT, two major regulators of neuronal survival and long-term plasticity in this brain structure. Animal models of depression have been developed as a way to study its neurobiology and to test

new therapeutic approaches (Cryan et al., 2002). One of these models is olfactory bulbectomy (Obx) (Song & Leonard, 2005), which mimics behavioral, physiological and neurochemical features of depression, such as deficits in learning and memory, reduced food-motivated selleck chemicals behavior, reduced libido, and stress hyperresponsiveness (Harkin et al., 2003; Song & Leonard, 2005; Deussing, 2006; Hellweg et al., 2007; Sato et al., 2010). These changes are usually observed 2 weeks after surgery (Mucignat-Caretta

et al., 2006), and are reversed by chronic, but not acute, antidepressant treatment (Harkin et al., CDK assay 2003; Song & Leonard, 2005; Song & Wang, 2010). Specifically, Obx results in a progressive degenerative process in limbic areas, and also produces neurodegeneration in the locus coeruleus and dorsal raphe nucleus, leading to dysfunction of the noradrenergic or serotonergic system (Harkin et al., 2003; Canbeyli, 2010), two of the main targets of antidepressant drugs (López-Muñoz & Alamo, 2009). Bulbectomised animals show various behavioral changes, including impairment of cognitive function and increased locomotor activity and exploratory behavior (Harkin et al., 2003; Breuer et al., 2007; Sato et al., 2010). Obx is widely accepted as a model of depression with many similarities to the agitated form of human depression (Harkin et al., 2003). In addition, drugs used for the treatment of Alzheimer’s Etofibrate disease alleviate the cognitive impairments induced by

Obx (Hozumi et al., 2003; Borre et al., 2012), making this model suitable for studying the cognitive deficits that accompany depressive symptoms. It has been postulated that deficiency of ω-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), could play a role in the pathophysiology of a wide range of psychiatric disorders, Alzheimer’s disease, and dementias (McNamara & Carlson, 2006; Calon & Cole, 2007; Borsonelo & Galduroz, 2008; Colangelo et al., 2009). Chronic ω-3 PUFA dietary deficiency reduces central serotonin [5-hydroxytryptamine (5-HT)] synthesis, suggesting that the provision of essential ω-3 fatty acids in early stages of cerebral development affects brain function permanently (McNamara et al., 2009).