Nesfatin-1 increases anxiety- and fear-related behaviors in the rat
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Nesfatin-1, derived from the protein NEFA/nucleobindin2 (NUCB2), is a newly identified peptide that acts as a potent satiety agent. It has been reported that peptides involved in the regulation of ingestive behavior are also involved in the regulation of the stress response. However, the relation between nesfatin-1 and stressor-related behaviors like anxiety and/or fear has not yet been investigated.
The effects of intracerebroventricular (ICV) injection of nesfatin-1 (0, 5, and 25 pmol/3 μl) were assessed in several paradigms that are thought to reflect anxiety and/or fear in rats.
Consistent with an anxiogenic effect, nesfatin-1 dose-dependently decreased the percentage of time spent on the open arms of the elevated plus maze, increased latency to approach, and decreased consumption of a palatable snack in an anxiogenic (unfamiliar) environment. Moreover, ICV nesfatin-1 increased the fear-potentiated startle response and the time spent freezing to both context and conditioned cues in a conditioned emotional response test.
These findings suggest that in addition to its role as a satiety peptide, nesfatin-1 may also be involved in the mediation of anxiety- and/or fear-related responses.
KeywordsNesfatin-1 Anxiety Fear Elevated plus maze Novelty Fear-potentiated startle Conditioned emotional response
This study was supported by funds from the Canadian Institutes of Health Research (CIHR) and the Natural Science and Engineering Research Council of Canada (NSERC). HA is a Canadian Research Chair in Neuroscience. All experiments were conducted in accordance with the current laws of Canada. None of the authors have any direct or indirect conflicts of interests of a financial nature relevant to the present work.
- File SE (1992) Behavioural detection of anxiolytic action. In: Elliot JM, Heal DJ, Marsden CA (eds) Experimental approaches to anxiety and depression. Wiley, Chichester, pp 25–44Google Scholar
- Fort P, Butaud C, Salvert D, Shimizu H, Hashimoto K, Mori M, Luppi PH (2007) The satiety molecule nesfatin-1 is co-localized with MCH in hypothalamic neurons expressing Fos during paradoxical sleep in rats. Société des Neuroscience (8e Colloque Montpellier) Abstract:B.13Google Scholar
- Kohno D, Nakata M, Maejima Y, Shimizu H, Sedbazar U, Yoshida N, Dezaki K, Onaka T, Mori M, Yada T (2008) Nesfatin-1 neurons in paraventricular and supraoptic nuclei of the rat hypothalamus coexpress oxytocin and vasopressin and are activated by refeeding. Endocrinology 149:1295–1301PubMedCrossRefGoogle Scholar
- Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, New YorkGoogle Scholar
- Rossi M, Kim MS, Morgan DG, Small CJ, Edwards CM, Sunter D, Abusnana S, Goldstone AP, Russell SH, Stanley SA, Smith DM, Yagaloff K, Ghatei MA, Bloom SR (1998) A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. Endocrinology 139:4428–4431PubMedCrossRefGoogle Scholar
- Ueta Y, Ozaki Y, Saito J, Onaka T (2003) Involvement of novel feeding-related peptides in neuroendocrine response to stress. Exp Biol Med 228:1168–1174Google Scholar
- Valles A, Marti O, Garcia A, Armario A (2000) Single exposure to stressors causes long-lasting, stress-dependent reduction of food intake in rats. Am J Physiol 279:R1138–R1144Google Scholar