Effects of disrupted ghrelin receptor function on fear processing, anxiety and saccharin preference in mice

• Published in: Psychoneuroendocrinology Vol. 110; p. 104430
• Main Authors: Pierre, A., Regin, Y., Van Schuerbeek, A., Fritz, E.M., Muylle, K., Beckers, T., Smolders, I.J., Singewald, N., De Bundel, D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2019
• Subjects: Animals; Anxiety - genetics; Anxiety - metabolism; Anxiety - physiopathology; Anxiety-like behavior; Conditioning, Psychological - drug effects; Conditioning, Psychological - physiology; Fear - psychology; Fear processing; Food Preferences - psychology; Gene Deletion; Ghrelin - physiology; Ghrelin resistance; High-fat diet; Hyperphagia - genetics; Hyperphagia - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Ghrelin - genetics; Receptors, Ghrelin - physiology; Saccharin - administration & dosage; Saccharin preference; EPM; HFD; FC-HFD; Ghrelin resistance; CBT; EBT; NPY; OF; cDNA; qPCR; AgRP; WT; US; CSDS; GHSR; Fear processing; KO; HAB; Anxiety-like behavior; i.p; CS; PTSD; ARC; HFD-FC; High-fat diet; HPA; SEM; Saccharin preference; ITI
• ISSN: 0306-4530; 1873-3360
• DOI: 10.1016/j.psyneuen.2019.104430

•Exposure to a high-fat diet reduces ghrelin receptor function.•Exposure to a high-fat diet does not alter fear or anxiety-like behaviour but lowers saccharin preference.•Loss of ghrelin receptor function does not alter fear or anxiety-like behaviour but lowers saccharin preference.
Obesity is a risk factor for stress-related mental disorders such as post-traumatic stress disorder. The underlying mechanism through which obesity affects mental health remains poorly understood but dysregulation of the ghrelin system may be involved. Stress increases plasma ghrelin levels, which stimulates food intake as a potential stress-coping mechanism. However, diet-induced obesity induces ghrelin resistance which in turn may have deleterious effects on stress-coping. In our study, we explored whether disruption of ghrelin receptor function though high-fat diet or genetic ablation affects fear processing, anxiety-like behavior and saccharin preference in mice.
Adult male C57BL6/J mice were placed on a standard diet or high-fat diet for a total period of 8 weeks. We first established that high-fat diet exposure for 4 weeks elicits ghrelin resistance, evidenced by a blunted hyperphagic response following administration of a ghrelin receptor agonist. We then carried out an experiment in which we subjected mice to auditory fear conditioning after 4 weeks of diet exposure and evaluated effects on fear extinction, anxiety-like behavior and saccharin preference. To explore whether fear conditioning as such may influence the effect of diet exposure, we also subjected mice to auditory fear conditioning prior to diet onset and 4 weeks later we investigated auditory fear extinction, anxiety-like behavior and saccharin preference. In a final experiment, we further assessed lack of ghrelin receptor function by investigating auditory fear processing, anxiety-like behavior and saccharin preference in ghrelin receptor knockout mice and their wild-type littermates.
High-fat diet exposure had no significant effect on auditory fear conditioning and its subsequent extinction or on anxiety-like behavior but significantly lowered saccharin preference. Similarly, ghrelin receptor knockout mice did not differ significantly from their wild-type littermates for auditory fear processing or anxiety-like behavior but showed significantly lower saccharin preference compared to wild-type littermates.
Taken together, our data suggest that disruption of ghrelin receptor function per se does not affect fear or anxiety-like behavior but may decrease saccharin preference in mice.