Nesfatin-130-59 Injected Intracerebroventricularly Increases Anxiety, Depression-Like Behavior, and Anhedonia in Normal Weight Rats.

Stephanie Kühne,York Winter,Miriam Goebel-Stengel,Andreas Stengel,Melissa Long,Tiemo Friedrich,Peter Kobelt,Martha Schalla,Matthias Rose,Marion Rivalan

doi:10.3390/nu10121889

Abstract

Nesfatin-1 is a well-established anorexigenic peptide. Recent studies indicated an association between nesfatin-1 and anxiety/depression-like behavior. However, it is unclear whether this effect is retained in obesity. The aim was to investigate the effect of nesfatin-130-59—the active core of nesfatin-1—on anxiety and depression-like behavior in normal weight (NW) and diet-induced (DIO) obese rats. Male rats were intracerebroventricularly (ICV) cannulated and received nesfatin-130-59 (0.1, 0.3, or 0.9 nmol/rat) or vehicle 30 min before testing. Nesfatin-130-59 at a dose of 0.3 nmol reduced sucrose consumption in the sucrose preference test in NW rats compared to vehicle (–33%, p < 0.05), indicating depression-like/anhedonic behavior. This dose was used for all following experiments. Nesfatin-130-59 also reduced cookie intake during the novelty-induced hypophagia test (−62%, p < 0.05). Moreover, nesfatin-130-59 reduced the number of entries into the center zone in the open field test (−45%, p < 0.01) and the visits of open arms in the elevated zero maze test (−39%, p < 0.01) in NW rats indicating anxiety. Interestingly, DIO rats showed no behavioral alterations after the injection of nesfatin-130-59 (p > 0.05). These results indicate an implication of nesfatin-130-59 in the mediation of anxiety and depression-like behavior/anhedonia under normal weight conditions, while in DIO rats, a desensitization might occur.

Highlights

Nesfatin-1 was identified in the rat hypothalamus and early on established as an anorexigenic peptide [1]
Nesfatin-130-59 injected in normal weight rats ICV at a dose of 0.3 nmol significantly reduced the sucrose/water intake ratio to 0.66 ± 0.13 (n = 11) compared to vehicle (1.00 ± 0.00, n = 11) and nesfatin-130-59 at a dose of 0.1 nmol (1.00 ± 0.00, p = 0.03; n = 10), while compared to nesfatin-130-59 at a dose of 0.9 nmol (0.88 ± 0.09, n = 10) did not reach significance (p = 0.30; Figure 1) reflective of an10, anhedonic effect
When nesfatin-130-59 was injected at 0.3 nmol in diet-induced obese (DIO) rats, no difference in sucrose intake was observed as reflected by a similar sucrose/water intake ratio in nesfatin-130-59 and vehicle treated rats (p = 0.69; n = 8/group, Figure 1)

Summary

Introduction

Nesfatin-1 was identified in the rat hypothalamus and early on established as an anorexigenic peptide [1]. Studies identified other effects of peripheral nesfatin-1 such as a role in glucose homeostasis [13], an anti-inflammatory action [14], and an increase of blood pressure [15] pointing towards more pleiotropic effects of the peptide, an assumption recently supported by the widespread distribution of nesfatin-1 autoradiographic signals [16], a surrogate parameter for the expression of the nesfatin-1 receptor which is still to be identified [17] These signals were detected in the gastric mucosa, duodenum, jejunum, ileum, pancreas, adrenal gland, testis, visceral adipose tissue, heart, skeletal muscle, lung, liver and kidney as well as in the pituitary, cortex, paraventricular nucleus of the hypothalamus, area postrema, dorsal motor nucleus of the vagus nerve and cerebellum [16]

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Results

Conclusion